Cardiac alpha-adrenoceptors: postjunctional and prejunctional.

Postjunctional alpha-adrenoceptors subserve positive inotropic and chronotropic responses. When beta-adrenoceptors are blocked, agonists that act on alpha 1-adrenoceptors evoke positive chronotropic responses in the pithed rat and rat isolated atria. The rank order of potency for this effect is adrenaline greater than noradrenaline greater than phenylephrine greater than methoxamine. The order of potency for antagonists to block the responses is prazosin greater than phentolamine greater than yohimbine. Thus, the postjunctional alpha-adrenoceptors are of the alpha 1-subtype. The positive chronotropic responses elicited by activating alpha 1-adrenoceptors have a slower time course than those elicited by activation of beta-adrenoceptors. When beta-adrenoceptors are blocked by propranolol, the positive chronotropic response to phenylephrine is enhanced by increasing the calcium concentration or by the calcium channel activator Bay K 8644 (0.1 microM), whereas the response is decreased by lowering the calcium concentration or by calcium antagonists (verapamil, nifedipine, nicardipine and diltiazem). Therefore, the positive chronotropic response to alpha 1-adrenoceptor activation involves an increased influx of calcium through calcium channels. Prejunctional alpha 1-adrenoceptors are involved in autoinhibitory feedback regulation of transmitter release from noradrenergic neurones. In rat atria, the release of noradrenaline induced by sympathetic nerve stimulation is inhibited by both clonidine and methoxamine, and is enhanced (by disruption of noradrenaline-mediated autoinhibition) by both idazoxan and prazosin. Thus, the prejunctional alpha-adrenoceptors are of both alpha 1- and alpha 2-subtypes. Drugs which produce blockade of postjunctional alpha 1-adrenoceptors could also produce an increase in neurogenic release of noradrenaline due to blockade of prejunctional alpha 1-adrenoceptors, and this might result in more complex effects than would be anticipated.