Effects of neurokinins on the isolated pig coronary artery

The actions of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY), kassinin (KAS) and eledoisin (ELE) were investigated on transversally cut strips of pig coronary artery. All tachykinins produced vasodilation of coronary arteries precontrracted with ACh; 10 −5 M. The order of potency was: SP = PHY ELE < KAS < NKA < NKB, with the ED 50 values being 0.38, 0.38, 1.2, 2.6, 8.3 and 34.0 nM, respectively. Continued superfusion of SP (7.4 × 10 −9 M) desensitized the coronary arteries which were refractory to the vasodilator action of NKA, NKB, PHY and KAS. The arteries nevertheless dilated upon the addition of noradrenaline (NA) and bradykinin (BK). Endothelium-removed preparations did not respond to any of the tachykinins. However, tissues devoid of endothelium relaxed in response to both NA and vasoactive intestinal polypeptide (VIP). Three octapeptide antagonists, [D-Pro 4,Ala 6,D-Trp 7,9,Nle 11]SP-(4–11) (compound I), [D-Pro 4,Ser 6,D-Trp 7,9,Nle 11]SP-(4–11) (compound II) and [D-Pro 4,D-Trp 7,9,10,Phe 11]SP-(4–11) (compound III) were examined as potential antagonists of tachykinin-induced vasodilatation. Compounds I and II blocked the actions of SP and NKA but not that of PHY. Compound III effectively blocked the actions of SP and PHY. We conclude that the pig coronary artery possesses a ‘NK-P/SP-P‘ type receptor, and that this receptor is probably localized on the endothelium.