Characterization of tachykinin receptors in isolated basilar arteries of guinea-pig.

In circular lengths cut from the basilar artery of guinea-pig (0.2-0.3 mm o.d.) relaxations induced by substance P and neurokinin A were highly susceptible to mechanical damage of the endothelium by rubbing. The precontraction induced by prostaglandin F2 alpha but not that of 124 mM potassium was reduced considerably by the rubbing procedure. Concentration-dependent relaxations were evoked by tachykinin agonists in the following order of potency: substance P = physalaemin greater than neurokinin A greater than eledoisin. Physalaemin was, however, a partial agonist, giving only half the maximum relaxation as compared to the other tachykinins. The two putative tachykinin receptor antagonists, spantide ([D-Arg1, D-Trp7,9, D-Leu11] substance P) and [D-Pro2, D-Trp7,9] substance P, shifted the concentration-dependent relaxations of substance P to the right in a parallel manner. Calculation of pA2 values and Schild plot analysis revealed pA2 values of 7.4-7.6 for spantide and 6.9-7.0 for [D-Pro2, D-Trp7,9] substance P, irrespective of whether substance P or neurokinin A was used as agonist. The pA2 values and the Schild plot analysis suggest a specific interaction between tachykinin agonists and antagonists that follow a simple bimolecular process. The results suggest the presence of tachykinin receptors of the 'SP-P' type in guinea-pig basilar arteries which, for induction of relaxation, involves the release of an endothelium-derived relaxing factor.