Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease

Patrick W Mantyh, C. R. Mantyh, T. Gates, S. R. Vigna, J. E. Maggio

Research output: Contribution to journalArticle

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Abstract

The mammalian tachykinins, substance P, substance K (neurokinin A) and neuromedin K (neurokinin B), are putative peptide neurotransmitters in both the brain and peripheral tissues. We used quantitative receptor autoradiography to localize and quantify the distribution of binding sites for radiolabeled substance P, substance K and neuromedin K in the canine gastrointestinal tract. Substance P binding sites were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, neurons in the myenteric plexus, mucosal epithelial cells, exocrine cells and lymph nodules. Substance K binding sites were distributed in a pattern distinct from substance P binding sites and were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, and neurons of the myenteric plexus. Neuromedin K binding sites were not observed in any area of the canine gastrointestinal tract although they were localized with high specific/non-specific binding ratios in the canine spinal cord. These results indicate that there are at least two distinct types of tachykinin receptor binding sites in the canine gastrointestinal tract, one of which probably recognizes substance P and the other substance K as endogenous ligands. In correlation with previous physiological data, these substance P and substance K receptor binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including gastric motility, mucosal ion transport, hemodynamics, digestive enzyme secretion and neuronal excitability. In addition these results demonstrate that receptor binding sites for substance P and substance K are expressed by cells involved in mediating inflammatory and immune responses. These data, together with our studies on surgical specimens from patients with inflammatory bowel disease, suggest that in a pathophysiological state tachykinins and their receptors may play a role in inflammatory bowel disease and should permit a rational approach to designing neuropeptide antagonists which may prove effective in treating inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)817-837
Number of pages21
JournalNeuroscience
Volume25
Issue number3
DOIs
StatePublished - 1988
Externally publishedYes

Fingerprint

Neurokinin A
Substance P
Inflammatory Bowel Diseases
Gastrointestinal Tract
Canidae
Neurokinin B
Binding Sites
Tachykinin Receptors
Myenteric Plexus
Venules
Arterioles
Smooth Muscle Myocytes
Endothelium
Smooth Muscle
Mucous Membrane
Neurokinin-2 Receptors
Neurons
Tachykinins
Ion Transport
Lymph

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease. / Mantyh, Patrick W; Mantyh, C. R.; Gates, T.; Vigna, S. R.; Maggio, J. E.

In: Neuroscience, Vol. 25, No. 3, 1988, p. 817-837.

Research output: Contribution to journalArticle

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