Functional characterization of substance P receptors in the rabbit ear artery

Rabbit isolated ear arteries were perfused at a constant flow and stimulated with field pulses (5 Hz, 5 impulses). Different tachykinins and capsaicin depressed stimulation-induced vasoconstriction, substance P (SP) being the most potent inhibitor. The rank order of potency of the tachykinins was, SP approximately equal to physalaemin approximately equal to eledoisin greater than SP-methyl ester; that of SP and its C-terminal fragments, SP approximately equal to SP-(2-11) approximately equal to SP-(4-11) greater than SP-(6-11). SP-(1-9) was inactive. The SP antagonist (Arg5,D-Trp7,9,Nle11)SP-(5-11) 10 mumol/l shifted the concentration-response curve of SP to the right (pA2 = 5.43), whereas it did not reduce the action of capsaicin. Another SP antagonist (D-Pro4,D-Trp7,9,10)SP-(4-11) 10 mumol/l failed to affect the SP depression. Neither antagonist changed vasoconstriction by itself. Pretreatment of the arteries with a mixture of yohimbine, propranolol, atropine, diphenhydramine, burimamide, methysergide and indomethacin, all 1 mumol/l, did not influence the effect of SP or capsaicin. Only the inhibition by SP, but not that by capsaicin was abolished after mechanical destruction of the endothelium. SP, physalaemin and eledoisin, all 3 mumol/l, reduced vasoconstriction by noradrenaline or histamine; capsaicin 30 mumol/l depressed noradrenaline-induced vasoconstriction. In arteries preincubated with 3H-noradrenaline, electrical stimulation (1 Hz, 120 pulses) triggered an increase in the outflow of tritium and evoked vasoconstriction. SP 1 mumol/l did not change either basal or stimulation-evoked tritium outflow, whereas it reduced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)