RECEPTOR MECHANISMS FOR 5‐HYDROXYTRYPTAMINE IN RABBIT ARTERIES

1 Previous investigations into the vascular actions of biogenic amines implicated in migraine have shown that the contractile effects of both 5‐hydroxytryptamine (5‐HT) and noradrenaline (NA) in the rabbit ear artery are mediated by a direct sympathomimetic action at α‐adrenoceptors, while in the rabbit aorta, 5‐HT and NA act on pharmacologically distinct receptors. The purpose of the present investigation was to determine whether the absence of 5‐HT receptors in rabbit ear arteries is characteristic of distributing arteries in general, or is confined to particular regional circulations. 2 Agonist‐antagonist interactions were studied in various rabbit vascular preparations (common carotid, external carotid and femoral arterial strips, and perfused ear arteries) by determining pA2 values for pizotifen and phentolamine against 5‐HT‐ and NA‐induced contractile responses. 3 In common carotid and femoral arteries, pizotifen was a potent competitive antagonist of 5‐HT, but weak against NA. The converse applied to phentolamine. In external carotid and ear arteries, pizotifen was a weak competitive antagonist of both 5‐HT and NA, whereas phentolamine was a potent competitive antagonist of both. Cocaine did not influence pA2 values against NA. 4 5‐HT and NA were of similar potency in common carotid and femoral arteries, but 5‐HT was much less potent than NA in external carotid and ear arteries. 5 The results indicate that rabbit common carotid and femoral arteries contain both D‐type 5‐HT receptors and α‐adrenoceptors, as does the aorta. However, external carotid arteries, like ear arteries, do not contain specific 5‐HT receptors. The action of 5‐HT in the external carotid artery is mediated by α‐adrenoceptors; this is a direct sympathomimetic action since it was not inhibited by cocaine or reserpine‐pretreatment. 5 6 The absence of 5‐HT receptors in the rabbit extracranial circulation may limit the usefulness of this species as a model for research relating to migraine.