A proposed mechanism for the biphasic vasoconstrictor responses to 5-hydroxytryptamine and methysergide in the rabbit...

Rabbit ear arteries were isolated and perfused at a constant flow rate so that the perfusate flowed into the fluid bathing the adventitial surface of the artery. Submaximal doses of intraluminally applied noradrenaline injected as a bolus into the perfusion fluid produced transient monophasic vascoconstrictor responses. In contrast, similarly administered 5-hydroxytryptamine (5-HT) or methysergide caused prolonged biphasic vascoconstrictor responses. The extraluminal/intraluminal potency ratios for noradrenaline, 5-HT and methysergide were 230, 15 and 6 respectively, which indicates that 5-HT methysergide are relatively more potent when administered extraluminally than noradrenaline. Cocaine (3-0 X 10(-5) mol litre-1) markedly increased the potency of extraluminally administered noradrenaline and converted the monophasic responses produced by noradrenaline to biphasic responses. It is concluded that under the experimental conditions used 5-HT and methysergide produced biphasic responses by an action on the medial smooth muscle firstly via the intraluminal surface and secondly an additional direct action via the adventitial surface. Noradrenaline's extraluminal potency is low because of its neuronal uptake and hence the responses are normally monophasic.