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.