Endothelium-dependent relaxant effect of neurokinins on rabbit aorta is mediated by the NK1 receptor.
Several neurokinins, namely substance P, neurokinin A, neurokinin B, [beta-Ala8]neurokinin A-(4-10) and senktide, were tested on noradrenaline-precontracted rabbit aortic rings to characterize the receptor mediating their endothelium-dependent relaxant effect in this preparation. CP-96,345, the new nonpeptide antagonist selective for the NK1 receptor, was also studied. Substance P, neurokinin A and neurokinin B, in that order of potency, were effective in relaxing precontracted rings, indicating the involvement of the NK1 receptor; [beta-Ala8]neurokinin A-(4-10) and senktide, which are selective agonists for NK2 and NK3 receptors, respectively, had no significant relaxant effect. The relaxant effects of substance P, neurokinin A and neurokinin B were competitively antagonized by nanomolar concentrations of CP-96,345. These findings support the view that the NK1 receptor mediates the endothelium-dependent relaxant effect of the neurokinins in rabbit aorta.
Rubino
A
A
Cardiovascular Research Department, Ciba-Geigy Ltd., Basle, Switzerland.
Thomann
H
H
Henlin
J M
JM
Schilling
W
W
Criscione
L
L
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007705:Kinins / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011817:Rabbits; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D001713:Biphenyl Compounds; D007705:Kinins; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C066892:CP 96345