title: Pharmacological evidence for the possible coexistence of multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.
abstract: Contractile responses to neurokinin alpha and neurokinin beta were characterized and compared with those to substance P (a SP-P agonist) and eledoisin (a SP-E agonist) in isolated rabbit iris sphincter. Neurokinin alpha and neurokinin beta as well as substance P and eledoisin produced atropine- and tetrodotoxin-resistant contractions of the iris sphincter in nanomolar concentrations, and the rank order of sensitivity was eledoisin greater than substance P = neurokinin alpha = neurokinin beta. After prolonged cold-storage of the preparations, responses to capsaicin, a releaser of tachykinins from sensory nerve endings, were nearly absent, but responses of considerable magnitude to carbachol and the tachykinins persisted. On wash-out of the tachykinins, responses faded at characteristic rates (neurokinin alpha greater than eledoisin greater than neurokinin beta much greater than substance P). From the Schild analyses, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P, a potent substance P antagonist, competitively antagonized the response to substance P, had no significant effect on the response to neurokinin beta, and antagonized the response to neurokinin alpha and eledoisin in a more complex manner. Taken together, these results suggest that there coexist multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004600:Eledoisin / Q000494:pharmacology; D066298:In Vitro Techniques; D007498:Iris / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D015288:Neurokinin A; D015287:Neurokinin B; D009479:Neuropeptides / Q000378:metabolism; D011817:Rabbits; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D013373:Substance P; D013779:Tetrodotoxin; D004600:Eledoisin; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; D015288:Neurokinin A; D015287:Neurokinin B; D002217:Carbachol