Sweating regulation through olfactory receptor

Abstract

To provide a sweating regulator or the like that is harmless for a human body and is useful for sweating regulation.SOLUTION: A sweating regulator contains an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a sweat regulating agent comprising an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15, and a sweat regulating agent. The present invention relates to a method for screening candidate substances for moderation agents. [Background technology]

[0002] Sweating is an important human physiological function for maintaining health. When sweating is reduced (anhidrosis), body temperature rises, leading to heatstroke and dry skin. When sweating is excessive (hyperhidrosis), body temperature decreases, making it difficult to engage in social activities, for example. As a method for controlling sweating, for example, a method of blocking sweat ducts with aluminum chloride is used in the case of hyperhidrosis, or a drug (anticholinergic agent) that suppresses the action of acetylcholine, which induces sweating, is used. However, aluminum chloride is likely to cause irritant dermatitis, and anticholinergic agents are likely to cause side effects such as dry eyes, dry mouth, headache, and tachycardia, so the range of application is not wide (Non-Patent Documents 1 and 2). In addition, a method for inducing sweating in anhidrosis has not yet been established. In light of this situation, the establishment of a more harmless and effective method for controlling sweating has been desired. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] S. Gregoriou et al., Clin Cosmet Investig Dermatol. 2019; 12: 733-744 [Non-Patent Document 2] I. Hoorens et al., J Eur Acad Dermatol Venereol. 2012; 26: 1-8 Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention provides a sweat regulating agent comprising an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15. Another object of the present invention is to provide a method for screening candidate substances for perspiration regulating agents. [Means for solving the problem]

[0005] The present inventors first hypothesized that there may be a difference in gene expression between the sweat glands in the non-hidrotic and sweating areas of anhidrosis patients, and that this difference may be causing anhidrosis. Therefore, the present inventors used sweat gland tissues from the non-hidrotic and sweating areas of anhidrosis patients to comprehensively analyze the genes expressed in the sweat glands by RNA sequencing. As a result, they surprisingly found that the sweat glands We found that olfactory receptors were expressed in the sweat glands of anhidrosis patients, and further investigated three types of olfactory receptors (OR6C74, OR51A7, and OR4A15) that showed significant differences in expression (p<0.01) between the sweat glands of anhidrosis patients and those of sweat glands of anhidrosis patients. As a result, we found that β-ionone (fragrance), an agonist for OR51E2, which is a related receptor of OR51A7, induced a quantitative axon reflex. In a perspiration test, the researchers discovered that α-ionone significantly increased the sweat rate (mg / min) of the subjects, while α-ionone (a fragrance), an antagonist of the receptor, decreased the sweat rate, leading to the completion of the present invention. This is what I came to do.

[0006] That is, the present invention relates to the following. [1] At least one olfactory receptor selected from the group consisting of OR6C74, OR51A7, and OR4A15. A sweat regulating agent comprising an agonist or antagonist for a receptor. [2] At least one selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15. The sweat regulating agent according to [1], which contains an agonist for a receptor. [3] The sweat regulating agent according to [1], wherein the sweat regulating agent is a sweat promoter. [4] The sweat regulating agent according to any one of [1] to [3], wherein the agonist is β-ionone. [5] At least one olfactory receptor selected from the group consisting of OR6C74, OR51A7, and OR4A15. The sweat regulating agent according to [1], which contains an antagonist against a receptor. [6] The sweat regulating agent according to [5], wherein the sweat regulating agent is an antiperspirant. [7] The sweating agent according to any one of [1], [5] and [6], wherein the antagonist is α-ionone. Regulator. [8] A method for screening a sweat regulating agent, comprising: (1) A test substance and a small number of olfactory receptors selected from the group consisting of OR6C74, OR51A7, and OR4A15. contacting the antibody with at least one receptor protein; (2) measuring the binding affinity between the test substance and the receptor protein; and (3) Using the measured binding property as an index, the test substance is selected as a candidate substance for a perspiration regulating agent. Selection process A screening method comprising: Effect of the Invention

[0007] According to the present invention, there is provided a sweat regulating agent comprising an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15. By using the agent of the present invention, it is possible to effectively control sweating in a manner that is harmless to the human body. Furthermore, according to the present invention, a screening method for candidate substances for sweating regulators can be provided using olfactory receptor proteins (hereinafter sometimes abbreviated as "olfactory receptors"), such as OR6C74 protein (hereinafter sometimes abbreviated as "OR6C74"), OR51A7 protein (hereinafter sometimes abbreviated as "OR51A7"), or OR4A15 protein (hereinafter sometimes abbreviated as "OR4A15"). By using the screening method of the present invention, it is possible to obtain substances that are harmless to the human body and can exert an effective sweating control effect. [Brief description of the drawings]

[0008] [Figure 1] Figure 1 shows the results of transcriptome analysis in sweating and non-sweating areas. [Diagram 2] FIG. 2 shows the effects of β-ionone on the olfactory receptors OR6C74, OR51A7, and OR4A15. [Diagram 3] FIG. 3 shows the effects of a compound other than β-ionone (α-ionone) on the olfactory receptors OR6C74, OR51A7, and OR4A15. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] 1. The perspiration regulator of the present invention The sweat regulating agent of the present invention contains an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15. In this study, "olfactory receptors" are defined as G protein-coupled receptors (hereinafter abbreviated as "GPCR"). These receptors belong to the class A rhodopsin-like receptors.

[0010] As used herein, "OR6C74" refers to an olfactory receptor protein (sequence number 2) classified as Olfactory Receptor Family 6 Subfamily C Member 74, and the nucleic acid encoding the protein is also referred to as the "OR6C74 gene" (sequence number 1). As used herein, "OR51A7" refers to an olfactory receptor protein (SEQ ID NO: 4) classified as Olfactory Receptor Family 51 Subfamily A Member 7, and the nucleic acid encoding the protein is also referred to as the "OR51A7 gene" (SEQ ID NO: 3). As used herein, "OR4A15" refers to Olfactory Receptor Family 4 Subfamily A Member It is an olfactory receptor protein (SEQ ID NO: 5) classified as er 15, and the nucleic acid encoding the protein is also referred to as the "OR4A15 gene" (SEQ ID NO: 6).

[0011] In the present invention, the term "agonist" refers to a substance that binds to a specific receptor and induces a reaction in a cell, and positive allosteric modulators (PAMs) are also included in agonists. An allosteric modulator refers to a molecule that binds to an allosteric site and exerts its action by enhancing or inhibiting the binding or signal transduction of an orthosteric ligand. Allosteric modulators are classified into PAMs and PAMs according to their effects on the activity of an orthosteric ligand, which correspond to enhancement, attenuation, or no change, respectively. Allosteric modulators can be classified into three types: NAM (Negative Allosteric Modulator), and SAM (Silent (or neutral) Allosteric Modulator). Suitable agonists contained in the agent of the present invention include, for example, β-ionone, pelargonic acid, and capric acid. The agent of the present invention contains agonists for specific receptors (R6C74, OR51A7, and OR4A15). When the sebum is absorbed into the skin, it functions as a sweat promoter. The sweat promoter may be, for example, a congenital / genetic or acquired It can be used for the prevention or treatment of congenital anhidrosis, preferably for the prevention or treatment of idiopathic anhidrosis, more preferably for the prevention or treatment of acquired idiopathic generalized anhidrosis. In addition, the sweat promoter can lower body temperature by sweating, so it can also be used for the treatment of heat stroke, for example. Furthermore, the sweat promoter can be used for the protection of dry skin caused by aging.

[0012] In the present invention, the term "antagonist" refers to a substance that reduces, inhibits, or prevents the action of another molecule or the activity of a receptor site. Antagonists also include competitive antagonists, non-competitive antagonists, uncompetitive antagonists, inhibitors of ion channels, and NAMs. Competitive antagonists include, but are not limited to, those that bind reversibly to the receptor at the same binding site (active site) as the endogenous ligand or agonist, but do not activate the receptor. Noncompetitive antagonists (also known as allosteric antagonists) bind to a site different from that of the agonist and act on the receptor via the other binding site. Noncompetitive antagonists do not compete with agonists for binding. A bound antagonist may reduce the affinity of the agonist for the receptor or may prevent the conformational changes of the receptor that are required for receptor activation after agonist binding. Uncompetitive antagonists differ from noncompetitive antagonists in that they require receptor activation by an agonist before binding to the allosteric binding site. Antagonists also include antibodies, aptamers, dominant negative mutants, and the like that inhibit the function of receptors or calcium channels. Suitable antagonists to be included in the agent of the present invention include, for example, α- Ionone, 2-ethylhexanoic acid. The agent of the present invention is an antagonist for specific receptors (R6C74, OR51A7, and OR4A15). When the composition contains the compound (I), it functions as an antiperspirant. The antiperspirant can be used, for example, in the prevention or treatment of hyperhidrosis and body odor.

[0013] The agent of the present invention can be incorporated into cosmetics or medicines (including quasi-drugs), or the agent of the present invention may itself be used as a cosmetic or medicine (including quasi-drugs).

[0014] When the agent of the present invention is incorporated into a cosmetic preparation, or when the composition of the present invention itself is used as a cosmetic preparation, examples of the types of cosmetic preparations include skin cosmetics such as facial cleanser, lotion, milky lotion, cream, gel, beauty serum, pack, mask, etc.; makeup cosmetics such as face powder, foundation, lipstick, blush, eyeliner, mascara, eye shadow, eyebrow ink, etc.; hair cosmetics such as shampoo, rinse, hair conditioner, hair styling agent, hair treatment, hair mist, etc.

[0015] When the agent of the present invention is blended with a cosmetic preparation, or when the agent of the present invention itself is used as a cosmetic preparation, The cosmetic may contain ingredients that may be added to ordinary cosmetic products to the extent that the effects of the present invention are not impaired. Specific examples of such ingredients include oils, chelating agents, surfactants, powders, sugar alcohols and their alkylene oxide adducts, lower alcohols, animal and plant extracts, nucleic acids, enzymes, anti-inflammatory agents, bactericides, preservatives, antioxidants, UV absorbers, antiperspirants, pigments, dyes, oxidation dyes, organic and inorganic powders, pH adjusters, pearlizing agents, wetting agents, etc.

[0016] Examples of oils include higher alcohols such as cetyl alcohol, isostearyl alcohol, lauryl alcohol, hexadecyl alcohol, and octyldodecanol; fatty acids such as isostearic acid, undecylenic acid, and oleic acid; esters such as myristyl myristate, hexyl laurate, decyl oleate, isopropyl myristate, hexyldecyl dimethyloctanoate, glycerin monostearate, diethyl phthalate, ethylene glycol monostearate, octyl oxystearate, alkyl benzoate, di(phytosteryl / octyldodecyl) lauroyl glutamate, and cetyl octanoate; Hydrocarbons such as liquid paraffin, polyisobutene, petrolatum, and squalane; waxes such as lanolin, reduced lanolin, and carnauba wax; oils and fats such as mink oil, cocoa oil, coconut oil, palm kernel oil, camellia oil, sesame oil, castor oil, and olive oil; ethylene-α-olefin-oligomers silicone oil, etc.

[0017] Particular examples of silicone oils include ether-modified silicones such as methylpolysiloxane, highly polymerized methylpolysiloxane, polyoxyethylene-methylpolysiloxane copolymer, polyoxypropylene-methylpolysiloxane copolymer, and poly(oxyethylene, oxypropylene)-methylpolysiloxane copolymer; stearoxytrimethylsilane, methylhydrogenpolysiloxane, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, tetrahydrotetramethylcyclotetrasiloxane, methylcyclopolysiloxane, and dodecamethylcyclohexylsiloxane. and cyclic silicones such as oxasiloxane; amino-modified silicones such as methylphenylpolysiloxane, trimethylsiloxysilicate, and aminoethylaminopropylsiloxane-dimethylsiloxane copolymer; alkoxy-modified polysiloxanes such as silanol-modified polysiloxane and stearoxymethylpolysiloxane, fatty acid-modified polysiloxane, fluorine-modified polysiloxane, epoxy-modified polysiloxane, alkoxy-modified polysiloxane perfluoropolyether, polyvinyl acetate dimethylpolysiloxane, and mixtures thereof.

[0018] The chelating agent is not particularly limited, but is preferably triethylenetetramine, 2-thenoyltrifluoroacetone, thioglycolic acid, tartaric acid, succinic acid, 8-quinolinol, pyridine-2,6-dicarboxylic acid, pyridine, 1,10-phenanthroline, lactic acid, 8-hydroxyquinoline-5-sulfonic acid, glycine, 2,2'-pyridylethylenediamine, aurintricarboxylic acid, xylenol orange, 5-sulfosalicylic acid, salicylic acid, pyrocatechol-3,5-dicarboxylic acid, or the like. Sulfonate, 4,5-dihydroxybenzene-1,3-disulfonic acid, 1,2-diaminocyclohexane San-N,N,N',N'-tetraacetic acid, citric acid, oxalate, nitrilotriacetic acid, ethylenediamine- and chelating agents selected from the group consisting of N,N,N',N-tetraacetic acid, acetylacetone and salts thereof, and mixtures thereof.

[0019] Examples of the surfactant include N-long chain acyl amino acid salts such as N-long chain acyl acidic amino acid salts and N-long chain acyl neutral amino acid salts, N-long chain fatty acid acyl-N-methyl taurine salts, alkyl esters, and alkyl esters. anionic surfactants such as alkyl sulfates and their alkylene oxide adducts, fatty acid amide ether sulfates, metal salts and weak base salts of fatty acids, sulfosuccinic acid surfactants, alkyl phosphates and their alkylene oxide adducts, and alkyl ether carboxylic acids; ether surfactants such as glycerin ethers and their alkylene oxide adducts, polyoxyethylene polyoxypropylene alkyl ethers, and other ether surfactants; alkylene oxide adducts of glycerin esters, alkylene oxide adducts of sorbitan esters, and polyoxyethylene polyoxypropylene alkyl ethers. Ether ester surfactants such as alkylene hydrogenated castor oil, ester surfactants such as polyoxyalkylene fatty acid esters, glycerin esters, fatty acid polyglycerin esters, sorbitan esters, and sucrose fatty acid esters, nitrogen-containing nonionic surfactants such as alkylglucosides, hydrogenated castor oil pyroglutamic acid diesters and their ethylene oxide adducts, and fatty acid alkanolamides; cationic surfactants such as alkyl ammonium chloride, dialkyl ammonium chloride, and other aliphatic amine salts, alkyl triethyl ammonium chloride, dialkyl dimethyl ammonium chloride, and other quaternary ammonium salts, aromatic quaternary ammonium salts such as benzalkonium salts, and fatty acid acyl arginine esters. and amphoteric surfactants such as betaine type surfactants, aminocarboxylic acid type surfactants, and imidazoline type surfactants.

[0020] Examples of the powder include resin powders such as nylon beads and silicone beads, nylon powder, metal fatty acid soap, yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, cobalt oxide, carbon black, ultramarine, Prussian blue, zinc oxide, titanium oxide, zirconium oxide, silicon oxide, aluminum oxide, cerium oxide, titanium mica, boron nitride, barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, magnesium silicate, silicon carbide, pigments, lake, sericite, mica, talc, kaolin, plate-shaped barium sulfate, butterfly-shaped barium sulfate, fine titanium oxide particles, fine zinc oxide particles, fine iron oxide particles, acyl lysine, acyl glutamic acid, acyl arginine, acyl glycine and other acyl amino acids, which may be further subjected to surface treatments such as silicone treatment, fluorine compound treatment, silane coupling agent treatment, silane-treated organic titanate treatment, acylated lysine treatment, fatty acid treatment, metal soap treatment, oil treatment, amino acid treatment, etc.

[0021] Examples of sugar alcohols and their alkylene oxide adducts include mannitol.

[0022] Examples of the lower alcohol include ethanol and propanol.

[0023] When the agent of the present invention is incorporated into a medicine (including quasi-drugs) or when the agent of the present invention itself is used as a medicine (including quasi-drugs), examples of the dosage form of the medicine include topical agents such as ointments (aqueous ointments, oily ointments, etc.), creams, solutions, emulsions, gels, lotions, liniments, pastes, etc.; adhesive agents such as poultices, plasters, tapes, patches, etc.; spray agents such as aerosols and sprays; suppositories, etc.

[0024] When the agent of the present invention is incorporated into a medicine (including quasi-drugs), or when the agent of the present invention itself is used as a medicine (including quasi-drugs), the medicine may contain pharmacologically acceptable carriers, excipients, diluents, soothing agents, preservatives, antioxidants, etc., within the scope of not inhibiting the effects of the present invention.

[0025] The agent of the present invention is a skin composition, and is preferably incorporated into a skin cosmetic or skin medicine (including quasi-drugs for skin), or the agent of the present invention itself is preferably a skin cosmetic or skin medicine (including quasi-drugs for skin). Here, "skin" is a concept that includes not only the epidermis of the body (e.g., face, head, neck, chest, abdomen, waist, back, buttocks, arms, legs, hands, etc.) but also mucous membranes, and "for skin" means application to the skin.

[0026] Examples of subjects to which the agent of the present invention can be applied include, but are not limited to, mammals (e.g., humans, mice, rats, hamsters, rabbits, cats, dogs, cows, sheep, monkeys, etc.).

[0027] The dosage of the agent of the present invention and the number of times it is administered to a subject depend on the form of the agent, the subject to which it is administered, and the body weight of the subject. It can be appropriately adjusted depending on the above.

[0028] In addition to the above, the agent of the present invention can be blended with, for example, a cleaning agent, or the agent of the present invention itself can be used as a cleaning agent.

[0029] When the detergent is a liquid detergent, the pH is usually 6 to 10, preferably 7 to 10, and more preferably 7.5 to 9.5. Within this range, a detergent composition with excellent usability can be provided. When the detergent is not a liquid, the pH is defined as the pH of a 10% aqueous solution (25°C) and conforms to the above pH range.

[0030] In the above-mentioned cleaning agent, various additives that are usually used can be added within a range that does not impair the effects of the present invention. For example, higher alcohols such as cetyl alcohol, stearyl alcohol, behenyl alcohol, isostearyl alcohol, octyldodecanol, oleyl alcohol, and myristyl alcohol, higher fatty acids such as hydrogenated beef tallow fatty acid, coconut oil fatty acid, and palm oil fatty acid and salts thereof (excluding fatty acids having 6 to 24 carbon atoms and salts thereof), trimethyl Examples of such ingredients include moisturizing agents such as glycine, surfactants such as anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants, vegetable oils, animal fats and oils, natural fat derivatives, mineral fats and oils, synthetic fats and oils such as lower and higher fatty acid esters, silicone compounds, polymeric substances, animal and plant extracts, amino acids, nucleic acids, vitamins, enzymes, anti-inflammatory agents, bactericides, preservatives, antioxidants, UV absorbers, chelating agents, antiperspirants, oxidative dyes, pH adjusters, pearlizing agents, etc., which are listed in various official compendia such as the Cosmetic Raw Materials Standards, Cosmetic Type Ingredient Standards, Quasi-Drug Raw Material Standards, Japanese Pharmacopoeia, Japanese Non-Pharmacopoeia Drug Ingredient Standards, and Food Additives Official Compendia.

[0031] Depending on the purpose of use, the above detergent can be used as shampoo, face wash, body shampoo, hand soap, shaving agent, kitchen detergent, or laundry detergent.

[0032] 2. Screening method for perspiration regulating agents of the present invention The screening method for a sweat regulating agent of the present invention includes the following steps: (1) A test substance and a small number of olfactory receptors selected from the group consisting of OR6C74, OR51A7, and OR4A15. contacting the antibody with at least one receptor protein; (2) measuring the binding affinity between the test substance and the receptor protein; and (3) Using the measured binding property as an index, the test substance is selected as a candidate substance for a perspiration regulating agent. Selection process The screening method includes:

[0033] The binding affinity of an olfactory receptor protein to a test substance (i.e., a candidate substance for a sweat regulator) may be measured, for example, by directly measuring the binding between the test substance and the olfactory receptor protein, or by measuring the activation of the olfactory receptor protein by the test substance and using the measured value as an index of binding. In addition, the method for measuring the binding affinity of an olfactory receptor protein to a test substance is not particularly limited as long as it can measure the above-mentioned binding or activation, and examples thereof include the following methods.

[0034] The binding between a test substance and an olfactory receptor protein can be measured by a known method for measuring the binding between substances, such as the binding between the protein and a ligand. Specifically, for example, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and the like can be used. Examples of such spectroscopy include surface plasmon resonance (SPR), nuclear magnetic resonance (NMR), and fluorescence correlation spectroscopy (FCS). do.

[0035] The activation of olfactory receptor proteins by a test substance can be measured, for example, by a known method for measuring the activity of receptors such as olfactory receptors. Examples of such methods include a calcium amount measurement method and an intracellular cAMP amount measurement method. The activation of olfactory receptor proteins by a test substance can be measured, for example, using the amount of intracellular calcium or the amount of intracellular cAMP as an indicator. For example, in HEK293T cells, olfactory receptors are activated by odorous components. When activated, it couples with intracellular G proteins (such as Golf) to activate adenylate cyclase, which activates cells. It is known to increase intracellular cAMP levels (Kajiya K. et al., Journal of Neuroscience, 2001, 21:6018-6025).

[0036] Methods for measuring the amount of intracellular cAMP include, for example, ELISA and reporter assay. Examples of the reporter assay include luciferase assay. According to the reporter assay, the amount of intracellular cAMP can be measured by using a reporter gene (luciferase gene, etc.) that is configured to be expressed depending on the amount of cAMP. Examples of the method for measuring the amount of intracellular calcium include calcium imaging and patch clamping. In calcium imaging, the amount of intracellular calcium can be measured by using a calcium indicator. Examples of the calcium indicator include calcium-sensitive fluorescent dyes and calcium-sensitive fluorescent proteins. Examples of the calcium-sensitive fluorescent dyes include Fura 2 and Fluo 4. Examples of the calcium-sensitive fluorescent proteins include Cameleon, TN-XL, GCaMP, and G-GECO.

[0037] The measured value of the binding activity of the olfactory receptor protein to the test substance (i.e., a candidate substance for a sweat regulating agent) obtained by the method described above can be compared with an appropriate standard value set in accordance with the desired degree of sweat regulating ability to select a candidate substance. EXAMPLES

[0038] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples in any way.

[0039] Example 1 Transcriptome analysis The sweating areas (skin with remaining sweating function) and anhidrosis areas (skin with impaired sweating function) of three anhidrosis patients Paraffin block samples of skin obtained from the skin samples were used, and sweat glands were collected by laser micro-dissection. Total RNA was extracted from the sweat glands using the Rneasy (registered trademark) FFPE kit (QIAGEN) according to the manufacturer's recommended protocol, and RNA sequencing was performed. Library preparation was performed using the TruSeq® Strand mRNA Sample Preparation Kit (Illumina) according to the manufacturer's recommended protocol. Sequencing was performed on a HiSeq® 2500 platform (Illumina). Casava® 1.8.2 software (Illumina) was used for base calling. Reads were aligned to the human genome reference information (http: / / www.illumina.com / ). When mapping to the A combination of Cufflinks (registered trademark) 2 ver 2.2.3 and SAMtools (registered trademark) ver. 0.1.19 was used. Mapped fragments were calculated using Cufflinks (registered trademark) ver. 2.2.1. Sweat glands in sweating and non-sweating areas of the same individual were compared, and genes whose RNA expression had changed by more than 2-fold with a p-value of <0.01 and in which the same change was observed in all three individuals were extracted. As a result, we found the presence of olfactory receptors (OR6C74, OR51A7, and OR4A15) that are expressed in sweating areas and whose expression is reduced in anhidrotic areas (Figure 1).

[0040] Example 2 Olfactory Receptor Evaluation Test 1 Olfactory receptors whose expression is decreased in anhidrotic areas found in Example 1 (OR6C74, OR51A7, and OR4A15) The sweat-related function of the olfactory receptor was evaluated using β-ionone, which selectively stimulates the olfactory receptor. A test to measure acetylcholine (Ach)-induced sweating using a real-time sweat meter. Axon reflex sweating test (QSART) was performed. The experimental method was as follows: one arm was given a mixture of base and β-ionone, and the other arm was given only the base. The amount of sweating per 5 minutes was measured on both the left and right sides at the same time. The arm that had the β-ionone-containing agent applied had a sweat rate of 1.829 mg / 5 min. When the base was used alone, the sweating rate was 0.568 mg / 5 min (Figure 2), which was approximately 3.22 times higher than that of the control. β-ionone acts as an agonist for olfactory receptors (OR6C74, OR51A7, and OR4A15). It was confirmed that the present invention can be used as a skin care product to promote sweating.

[0041] Example 3 Olfactory Receptor Evaluation Test 2 Effects of compounds other than β-ionone on olfactory receptors (OR6C74, OR51A7, and OR4A15) In order to evaluate the above, a QSART test was conducted. The test was carried out in the same manner as in Example 2, except that the above-mentioned was used. As can be seen from the results, the arm to which the agent containing the base and α-ionone was applied had a sweat rate of 1.182 mg / 5 min, while the arm to which the agent containing the base alone was applied had a sweat rate of 2.119 mg / 5 min (FIG. 3), which is about 0.56 times lower than the arm to which the agent containing the base alone was applied. From these results, it was found that α-ionone can be used as an antagonist against olfactory receptors (OR6C74, OR51A7, and OR4A15) and can suppress sweating. [Industrial Applicability]

[0042] The sweat regulating agent of the present invention, which contains an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15, is harmless to the human body. and can be used to provide effective sweat control.

Claims

1. A method for screening a sweat regulating agent, comprising: (1) contacting a test substance with at least one receptor protein selected from the group consisting of olfactory receptors OR51E2, OR51A7, OR6C74, and OR4A15; (2) measuring the binding affinity between the test substance and the receptor protein; and (3) selecting the test substance as a candidate substance for a perspiration regulating agent based on the measured binding property. A screening method comprising:

2. Step (1) is a step of contacting a test substance with at least one receptor protein selected from the group consisting of olfactory receptors OR51E2 and OR51A7; The screening method according to claim 1.

3. Step (1) is a step of contacting a test substance with a receptor protein of the olfactory receptor OR51E2; The screening method according to claim 1.

4. The screening method according to any one of claims 1 to 3, wherein in step (1), the test substance is a fragrance.

5. In step (3), a test substance whose measured binding ability indicates agonistic activity against a receptor is selected as a candidate substance for a sweat promoter. The screening method according to any one of claims 1 to 4.

6. In step (3), a test substance whose measured binding ability indicates antagonist activity against the receptor is selected as a candidate substance for an antiperspirant. The screening method according to any one of claims 1 to 4.

7. A skin perspiration promoter that contains β-ionone as a perspiration-promoting ingredient.

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