Olfactory receptor-mediated sweating control

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 sweating regulator containing an agonist or antagonist for at least one receptor selected from the group consisting of olfactory receptors OR6C74, OR51A7, and OR4A15, and a sweating regulator. The present invention relates to a method for screening candidate substances for health-saving agents. [Background technology]

[0002] Sweating is an important human physiological function for maintaining health. Decreased sweating (anhidrosis) leads to an increase in body temperature, heatstroke, and dry skin. Excessive sweating (hyperhidrosis) can lead to hypothermia, making social activities difficult, for example. To control sweating, for example, in the case of hyperhidrosis, methods such as blocking sweat ducts with aluminum chloride or drugs that suppress the action of acetylcholine, which induces sweating (anticholinergics), are used. However, aluminum chloride is likely to cause irritant dermatitis, and anticholinergics are likely to cause side effects such as dry eyes, dry mouth, headache, and tachycardia, so their range of application is limited (Non-Patent Documents 1 and 2). Furthermore, there is currently no established method for inducing sweating in anhidrosis. Given this situation, the development of a more harmless and effective method for controlling sweating is 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 considered that there may be differences in gene expression between sweat glands in the anhidrosis and sweat glands of anhidrosis patients, and that these differences may be causing anhidrosis. Therefore, the present inventors used sweat gland tissues from the anhidrosis and sweat glands 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 are expressed in sweat glands of anhidrotic patients, and further investigated three types of olfactory receptors (OR6C74, OR51A7, and OR4A15) that showed significant differences in expression (p<0.01) between the anhidrotic and hidrotic areas. As a result, we found that β-ionone (fragrance), an agonist for OR51E2, a receptor related to OR51A7, inhibited quantitative axon reflex responses. In a perspiration test, the researchers discovered that α-ionone significantly increased the sweat rate (mg / min), 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 happened.

[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 Sweat-regulating agents, including agonists or antagonists to receptors. [2] 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 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 to 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: [Effects 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, the present invention provides a screening method for candidate substances for sweating regulators 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"). Use of the screening method of the present invention makes it possible to obtain substances that are harmless to the human body and can exert effective sweating control effects. [Brief explanation of the drawings]

[0008] [Figure 1] Figure 1 shows the results of transcriptome analysis in sweating and non-sweating areas. [Figure 2] FIG. 2 shows the effects of β-ionone on the olfactory receptors OR6C74, OR51A7, and OR4A15. [Figure 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 INVENTION

[0009] 1. The sweat 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 context, "olfactory receptors" are G protein-coupled receptors (hereinafter abbreviated as "GPCRs"). These receptors belong to the rhodopsin-like receptors class A, more specifically.

[0010] As used herein, "OR6C74" refers to an olfactory receptor protein (SEQ ID NO: 2) classified as Olfactory Receptor Family 6 Subfamily C Member 74, and the nucleic acid encoding this protein is also referred to as the "OR6C74 gene" (SEQ ID NO: 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 this 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 this 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 response within a cell, and positive allosteric modulators (PAMs) are also included in the term 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 according to their effect on the activity of the orthosteric ligand, which can be enhanced, attenuated, or left unchanged. They can be classified into NAM (Negative Allosteric Modulator), 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 an agonist for specific receptors (R6C74, OR51A7, and OR4A15). When the compound is present in the skin, it functions as a perspiration promoter. The perspiration promoter may be, for example, a congenital / genetic or acquired perspiration promoter. The perspiration promoter 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. Furthermore, since the perspiration promoter can lower body temperature by sweating, it can also be used for the treatment of heat stroke, for example. Furthermore, the perspiration promoter can also be used to protect 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. Examples of antagonists include, but are not limited to, competitive antagonists that reversibly bind to receptors at the same binding site (active site) as endogenous ligands or agonists but do not activate the receptor. Noncompetitive antagonists (also known as allosteric antagonists) bind to a site different from the agonist's binding site and act on the receptor via another 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 prevent the conformational changes in the receptor 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 for inclusion in the agent of the present invention include, for example, α- Ionone, 2-ethylhexanoic acid. The agent of the present invention is an antagonist of specific receptors (R6C74, OR51A7, and OR4A15). The antiperspirant can be used, for example, to prevent or treat 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 cosmetics, or when the composition of the present invention itself is used as a cosmetic, examples of the types of cosmetics include skin cosmetics such as facial cleansers, lotions, milky lotions, creams, gels, beauty serums, packs, and masks; makeup cosmetics such as face powder, foundation, lipstick, blush, eyeliner, mascara, eye shadow, and eyebrow pencil; and hair cosmetics such as shampoos, rinses, hair conditioners, hair styling agents, hair treatments, and hair mists.

[0015] When the agent of the present invention is blended into a cosmetic, or when the agent of the present invention itself is used as a cosmetic, The cosmetic may contain ingredients that may be added to ordinary cosmetic preparations 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, disinfectants, preservatives, antioxidants, UV absorbers, antiperspirants, pigments, colorants, oxidation dyes, organic and inorganic powders, pH adjusters, pearlizing agents, humectants, 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 co-oligomers silicone oils, 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 methylphenylpolysiloxane, trimethylsiloxysilicate, and aminoethylaminopropylsiloxane-dimethylsiloxane copolymer; and silicone oils selected from the group consisting of alkoxy-modified polysiloxanes such as silanol-modified polysiloxanes and stearoxymethylpolysiloxanes, fatty acid-modified polysiloxanes, fluorine-modified polysiloxanes, epoxy-modified polysiloxanes, alkoxy-modified polysiloxane perfluoropolyethers, polyvinyl acetate dimethylpolysiloxanes, and mixtures thereof.

[0018] The chelating agent is not particularly limited, but preferred are 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, and pyrocatechol-3,5-dicarboxylic acid. Sulfonate, 4,5-dihydroxybenzene-1,3-disulfonic acid, 1,2-diaminocyclohexane San-N,N,N',N'-tetraacetic acid, citric acid, oxalate, nitrilotriacetic acid, ethylenediamine- Included are chelating agents selected from the group consisting of N,N,N',N-tetraacetic acid, acetylacetone and salts thereof, and mixtures thereof.

[0019] Examples of surfactants 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 acrylates, and alkyl acrylates. 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, and polyoxyethylene polyoxypropylene alkyl ethers; 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, alkyl glucosides, hydrogenated castor oil pyroglutamic acid diesters and their ethylene oxide adducts, and nitrogen-containing nonionic surfactants such as fatty acid alkanolamides; fatty amine salts such as alkyl ammonium chloride and dialkyl ammonium chloride, quaternary ammonium salts such as alkyl triethyl ammonium chloride and dialkyl dimethyl ammonium chloride, aromatic quaternary ammonium salts such as benzalkonium salts, and fatty acid acyl arginine esters. and amphoteric surfactants such as betaine surfactants such as carboxybetaine, aminocarboxylic acid surfactants, and imidazoline surfactants.

[0020] Examples of powders 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, and the like, which may be further surface-treated by 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 alkylene oxide adducts thereof 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 preparations such as ointments (aqueous ointments, oily ointments, etc.), creams, liquids, emulsions, gels, lotions, liniments, and pastes; adhesive preparations such as poultices, plasters, tapes, and patches; spray preparations such as aerosols and sprays; and suppositories.

[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 limits that do not inhibit 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 pharmaceutical (including quasi-drugs for skin), or the agent of the present invention itself is preferably made into a skin cosmetic or skin pharmaceutical (including quasi-drugs for skin). Here, "skin" is a concept that encompasses 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 and frequency of administration of the agent of the present invention to a subject depend on the form of the agent, the subject to which it is applied, and the body weight of the subject. It can be adjusted appropriately depending on the above.

[0028] In addition to the above, the agent of the present invention can also be incorporated into, for example, a detergent, or the agent of the present invention itself can be used as a detergent.

[0029] When the detergent is a liquid, 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] Various commonly used additives can be added to the above-mentioned cleansing agent as long as they do 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, disinfectants, preservatives, antioxidants, UV absorbers, chelating agents, antiperspirants, oxidative dyes, pH adjusters and pearlizing agents, etc., which are listed in various official standards such as the Standards for Cosmetic Raw Materials, Standards for Ingredients by Cosmetic Type, Standards for Quasi-drug Raw Materials, Japanese Pharmacopoeia, Standards for Ingredients of Non-Pharmacopoeia Drugs in Japan, and the Official Standards for Food Additives.

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

[0032] 2. Screening method for perspiration regulators of the present invention The method for screening a sweat regulating agent of the present invention comprises 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 A screening method comprising:

[0033] The binding affinity of an olfactory receptor protein to a test substance (i.e., a candidate substance for a sweat regulator) can 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. Furthermore, 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 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 (SPRM), and the like can be used. Examples 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 methods for measuring olfactory receptor proteins include calcium levels and intracellular cAMP levels. The activation of olfactory receptor proteins by a test substance can be measured using, for example, the amount of intracellular calcium or the amount of intracellular cAMP as an indicator. For example, in HEK293T cells, olfactory receptors are activated by aroma compounds. When activated, it couples with intracellular G proteins (such as Golf) to activate adenylate cyclase, 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 reporter assays include luciferase assays. Reporter assays can measure the amount of intracellular cAMP using a reporter gene (such as a luciferase gene) that is constructed so that its expression depends on the amount of cAMP. Methods for measuring the amount of intracellular calcium include calcium imaging and patch clamping. In calcium imaging, the amount of intracellular calcium can be measured using a calcium indicator. Examples of calcium indicators include calcium-sensitive fluorescent dyes and calcium-sensitive fluorescent proteins. Examples of calcium-sensitive fluorescent dyes include Fura 2 and Fluo 4. Examples of 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 sweating regulator) obtained by the method described above can be used to select a candidate substance by setting an appropriate standard value in accordance with the desired degree of sweating regulation ability and comparing the measured value with the standard value. [Example]

[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 area (skin with remaining sweating function) and the anhidrotic area (skin with impaired sweating function) of three anhidrotic patients Using paraffin block samples of skin obtained from the skin (skin), sweat glands were collected by laser microdissection. 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 (HGU). When mapping to the A combination of SAMtools (registered trademark) 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 the sweating and non-sweating areas of the same individual were compared, and genes whose RNA expression changed by 2-fold or more with a p-value of <0.01 and in which the same change was observed in 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 (OR6C74, OR51A7, and OR4A15) whose expression is decreased in anhidrotic areas found in Example 1 ) to selectively stimulate the olfactory receptors, and the sweat-related function of the olfactory receptors was evaluated using β-ionone. A test to measure acetylcholine (Ach)-stimulated sweating using a real-time sweat meter. The sudomotor axon reflex test (QSART) was performed. The experimental method was as follows: one arm was given a drug containing the base and β-ionone, and the other arm was given the base The amount of sweating per 5 minutes was measured on both the left and right sides at the same time. The arm to which the β-ionone-containing agent was applied had a sweat rate of 1.829 mg / 5 min, compared with With the base alone, the sweating rate was 0.568 mg / 5 min (Figure 2), which was approximately 3.22 times higher. β-ionone acts as an agonist for olfactory receptors (OR6C74, OR51A7, and OR4A15). It was confirmed that the product can be used as a moisturizer and promotes 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 carried out. The test was conducted in the same manner as in Example 2, except that the agent containing the base and α-ionone was used. As can be seen from the results, the sweat rate on the arm to which the agent containing the base and α-ionone was applied was 1.182 mg / 5 min, while the sweat rate on the arm to which the agent containing the base alone was 2.119 mg / 5 min (Figure 3), a reduction of approximately 0.56 times. These results demonstrate that α-ionone can be used as an antagonist for 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. 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) A step of selecting the test substance as a candidate substance for a perspiration regulating agent using the measured binding property as an index. 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 the 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 containing beta-ionone as a perspiration-promoting ingredient.

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