NEUROKININ RECEPTORS (NK1, NK2) IN THE MOUSE - A PHARMACOLOGICAL STUDY

Experiments were performed on strips of mouse stomach and urinary blad der to characterize the receptors involved in the contractile response s of these tissues to neurokinins (substance P (SP), neurokinin A (NKA ), neurokinin B (NKB), and neuropeptide gamma (NP gamma)). The neuroki nin receptors were characterized by using assays with selective agonis ts as well as peptide and nonpeptide antagonists and by applying the t wo Schild criteria for receptor classification, namely, the order of p otency of agonists and the apparent affinity of competitive antagonist s. The mouse stomach contains primarily NK1 and NK2 functional sites a nd possibly some NK3 receptors, whereas the urinary bladder possesses only the NK2 receptor. The rank order of potency of agonists in the st omach is Ac[Arg(6),Sar(9),Met(O-2)(11)]SP-(6-11) > NKA > SP > [beta-Al a(8)]NKA-(4-10) > NKB > [MePhe(7)]NKB. Among the selective agonists, A c[Arg(6),Sar(9),Met(O-2)(11)]SP-(6-11) is more active than SP and [Sar (9),Met(O-2)(11)]SP on the NK1 receptor, whereas the order of potency on the NK2 receptor is NKA > NP gamma greater than or equal to [beta-A la(8)]NKA-(4-10) > [Nle(10)]lNKA-(4-10). The order of potency of agoni sts in the bladder is NP gamma > NKA > [beta-Ala(8)]NKA-(4-10). The my otropic responses mediated by NK1 selective agonists are blocked by SR 140333 (pA2 8.57) and those mediated by the NK2 selective agonists ar e inhibited by SR 48968 (pA2 9.05). RP 67580 (pA2 8.41) is more active than CP 99994 (pA2 6.06) on the mouse NK1 receptor. The NK1 receptor of the mouse shows, therefore, a pharmacological profile similar to th at of the NK1 receptor of the rat. Similarly, MEN 10627 (pA2 9.20) is more active than R 396 (pA2 6.21), suggesting that the mouse NK2 recep tor is similar to that of the rabbit. The mouse NK2 receptor of the ur inary bladder shows similarity with that of the stomach, but is less s ensitive to [beta-Ala(8)]NKA-(4-10).