Elsevier

Peptides

Volume 10, Issue 3, May–June 1989, Pages 627-645
Peptides

Article
Receptors for sensory neuropeptides in human inflammatory diseases: Implications for the effector role of sensory neurons

https://doi.org/10.1016/0196-9781(89)90154-XGet rights and content

Abstract

Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-α, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.

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      However, in chronic inflammatory bowel diseases, tachykinin NK1 receptors have been found markedly upregulated, compared to their density measured in the intestine of normal subjects. Upregulation involves either sites where NK1 receptors are normally present (e.g., vasculature, epithelial cells), or even sites where they are normally absent (ectopic expression: e.g., in intestinal lymphoid aggregates) [197,232]. Recently, Renzi and coworkers [233] have shown that, in addition to NK1, also NK2 receptor expression is markedly increased on inflammatory cells (eosinophils) of the lamina propria of patients with Crohn’s disease or ulcerative colitis, suggesting their possible involvement in the above pathologies.

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    This work supported by the Southern California Arthritis Foundation, Sloan Foundation and NS-23970, NS-22961, DK-40260.

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