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Purpose of agonist of natriuretic peptide receptor A in pain management

A technology of receptor agonists and natriuretic peptides, which is applied in the fields of biotechnology and medicine, can solve the problems of unclear whether there is a relationship between pain, non-natriuretic peptides and their receptor expression and function research, etc.

Inactive Publication Date: 2012-03-14
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] However, the expression and function of natriuretic peptides and their receptors (such as B-type natriuretic peptide and natriuretic peptide receptor A) in the peripheral nervous system have never been studied in the field, and it is unclear whether there is a relationship between them and pain. relation

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  • Purpose of agonist of natriuretic peptide receptor A in pain management
  • Purpose of agonist of natriuretic peptide receptor A in pain management
  • Purpose of agonist of natriuretic peptide receptor A in pain management

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0163] Example 1. B-type natriuretic peptide and natriuretic peptide receptor A are expressed in dorsal root ganglia and expression increases after inflammation

[0164] Total RNA of L4 and L5 dorsal root ganglia of normal rats and rats 0.5, 2, 4, 7 and 14 days after CFA injection was used for Agilent 22k rat oligo gene chip analysis. Gene expression data were filtered and statistically analyzed.

[0165] Of the 20,500 gene probes tested, a total of 1257 gene probes (6.1% of the total probes) were identified as having significant expression changes, i.e., at least one of the five time points tested The detected gene expression was up-regulated or down-regulated by more than 2 times compared with normal tissue. Further unigene analysis identified 1123 genes represented by these probes (509 increased expression and 614 decreased expression), including 18 neuropeptides, 6 G protein-coupled receptors (G-protein-coupled receptors, GPCRs) and a natriuretic peptide receptor (Burbac...

Embodiment 2

[0170] Example 2. B-Type Natriuretic Peptide and Natriuretic Peptide Receptor A Expression in Dorsal Root Ganglion Microneurons and Increased Expression After Inflammation

[0171] The inventors further studied the cell distribution of B-type natriuretic peptide and natriuretic peptide receptor A in the dorsal root ganglion of rats by using immunohistochemistry.

[0172] The results showed that: B-type natriuretic peptide and natriuretic peptide receptor A are mainly distributed in the small neurons of the dorsal root ganglion (cross-sectional area figure 2 A and 2B). 50% of dorsal root ganglion neurons were immunopositive for B-type natriuretic peptide; 26% of dorsal root ganglion neurons were positive for natriuretic peptide receptor A ( figure 2 A). On day 2 of plantar injection of CFA, the intensity of B-type natriuretic peptide and natriuretic peptide receptor A immunofluorescence intensity of dorsal root ganglion neurons increased ( figure 2 A-C), while the number o...

Embodiment 3

[0176] Example 3. B-type natriuretic peptide reduces neuronal excitability in the presence of glutamate

[0177] The inventors further investigated whether B-type natriuretic peptide can regulate the electrical activity of small neurons in the dorsal root ganglion.

[0178] Previous studies have shown that activated natriuretic peptide receptor A induces the synthesis of cGMP and activates the downstream PKG so that the potassium channel BK Ca Phosphorylated, increasing the opening capacity of these channels, resulting in hyperpolarization of vascular smooth muscle cells and glomerular mesangial cells (Williams et al., 1988, Proc Natl Acad Sci USA85: 9360-9364; Sansom and Stockand, 1996, Clin Exp Pharmacol Physiol 23:76-82; Tanaka et al., 1998, Naunyn Schmiedebergs Arch Pharmacol 357:705-708). Importantly, applying the potassium channel BK Ca The channel opener NS1619 has been reported to reduce dorsal root ganglion small neuron firing frequency (Zhang et al., 2003, Neurosci...

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Abstract

The invention provides a purpose of an agonist of natriuretic peptide receptor A (NPR-A) in pain management. Specifically, the invention relates to a purpose of the NPR agonist in the preparations of medicine compositions used for releasing or treating pains. Preferably the agonist is B-type natriuretic peptide (BNP) or atrial natriuretic peptide (ANP). The invention also relates to a medicine composition containing the NPR-A agonist, and a method for screening potential substances that can be used for releasing or treating pains. According to the method, for the first time, a relation between NPR-A mediated NPR-A / PKG / BKCa approach and pains is disclosed; and a medicine, a method and a purpose for treating, releasing or ameliorating pains through the regulation of the activation of the approach are provided.

Description

technical field [0001] The invention belongs to the fields of biotechnology and medicine. More particularly, the present invention relates to the use of a natriuretic peptide receptor agonist, preferably an agonist of natriuretic peptide receptor A (eg B-type natriuretic peptide or atrial natriuretic peptide), in the treatment of pain. Background technique [0002] Pain is an unpleasant reaction of the body to damaged tissue or potential damage. It is a complex physiological and psychological activity and one of the most common clinical symptoms. It consists of pain sensation and pain response. It includes the pain sensation caused by noxious stimuli acting on the body, and the body's pain response to noxious stimuli (body motor response and / or visceral vegetative response, often accompanied by strong emotional color). [0003] Pain can be used as a warning that the body is injured, causing a series of defensive protective reactions of the body. But on the other hand, som...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K38/22A61K49/00A61P29/00A61P25/04
Inventor 张旭张方雄刘兴君鲍岚
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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