Functional subtyping of neurokinin receptors on canine proximal colonic mucosa
Crowther, R.; Jukic, D.; Regoli, D.; Rangachari, P.K.
Journal of Pharmacology and Experimental Therapeutics 268(3): 1374-1380
1994
ISSN/ISBN: 0022-3565 PMID: 7511164 Document Number: 437734
Functional subtyping of the receptors responsible for the neural and nonneural effects of substance P (SP) on the canine proximal colon were studied. Selective agonists and antagonists were used with two different in vitro preparations. The mucosa contained the muscularis mucosa and attendant submucosal plexuses, whereas the epithelium was devoid of both. We obtained the following results: (Sar-9,Met(02)-11)SP (Sar-9SP), a neurokinin-1 receptor agonist, stimulated both preparations; senktide, a neurokinin-3 agonist, evoked a response only on the mucosal preparation; (beta-Ala-8)NKA-4-10, a neurokinin-2 agonist, was ineffective on both preparations; tetrodotoxin completely inhibited the mucosal responses to senktide, but the inhibitory effects on Sar-9SP were only partial; CP-96,345, a neurokinin-1-selective antagonist, inhibited both epithelial and mucosal responses to Sar-9SP and R487 (Trp-7,beta-Ala-8)NKA-4-10, a neurokinin-3 antagonist, inhibited mucosal responses to senktide. Thus, the neural effects involved both neurokinin-1 and neurokinin-3 receptors, whereas the nonneural effects were mediated by neurokinin-1 receptors alone. Neurokinin-2 receptors were functionally absent.