THE TACHYKININ RECEPTORS INDUCING CONTRACTILE RESPONSES OF CANINE ILEUM CIRCULAR MUSCLE

This study sought to determine which tachykinin receptors were involve d in contractile responses of circular muscle to tachykinins infused i nto isolated segments of canine ileum. Selective agonists for neurokin in receptors NK1 and NK2 as well as for substance P (SP) and neurokini n A (NKA) were infused, and selective antagonists against NK1, NK2, an d NK3 receptors were tested. The responses to a submaximal concentrati on of NKA were reduced by a selective NK2 antagonist, SR-48968, and ab olished by a combination of this antagonist with an NK1 antagonist, ei ther CP-96,345 or RP-67580. The selective NK2 agonist, [Nle(10)]NKA-(4 -10), had low potency. We concluded that NKA acted on typical NK2 rece ptors and that its action was potentiated by its additional action on NK1 receptors. Neither the contractile responses to SP nor those to [S ar(9),Met(O-2)(11)]SP given in submaximal concentrations were inhibite d by CP-96,345 or RP-67580, either alone or together with SR-48968. In deed, the two NK1-selective antagonists potentiated responses to the s elective NK1 agonist, [Sar(9),Met(O-2)(11)]SP, an effect attributed to previously demonstrated prejunctional inhibitory action of the agonis t. The selective NK3 agonist, succinyl-[Asp(6),N-Me-Phe(8)]SP-(6-11), was not effective as a contractile agent, even after block of nitric o xide synthase with N-omega-nitro-L-arginine. The selective NK3 antagon ist, R-487, was also ineffective in blocking responses to SP. Studies with an antagonist to H-1 histamine receptors suggested that contracti le actions of SP did not involve histamine release from mast cells. We concluded that, in addition to typical NK1 and NK2 receptors activate d by NKA and a prejunctional inhibitory receptor activated by SP and [ Sar(9),Met(O-2)(11)]SP, another tachykinin receptor existed on canine ileum to initiate contractions. It is not a typical NK1, NK2, or NK3 r eceptor.