Radioligand binding studies of adrenergic receptors and their clinical relevance.

Ahlquist in 1948 first recognised that there were two distinct types of adrenoceptor, which he was able to differentiate by comparing the rank order of potency of several adrenergic agonists in various tissues.1 Alpha-adrenoceptors which mediate smooth muscle contraction were characterised by the potency order adrenaiine> noradrenaline >isoprenaline and beta adrenoceptors, mediating relaxation, by the rank order isoprenaline > adrenaline > noradrenaline. Since then specific antagonists such as phentolamine, which blocks a-adrenorecep tors, and propranalol, which blocks ?-adrenoreceptors3 have been developed. Beta-adrenoceptors have been subclassified into ?x-receptors, which mediate positive inotropic cardiac re? sponses and lipolysis and for which adrenaline and noradrena? line are equipotent, and ?o-receptors, which mediate relaxation in vascular, bronchial, and uterine smooth muscle for which adrenaline is more potent than noradrenaline.2 Antagonists such as practolol, atenolol, and metroprolol are more potent at ?x than ?2-receptors (and are therefore termed cardioselective), whereas agonists such as salbutamol and terbutaline are more potent at ?2than ?rreceptors (and are therefore termed bronchodilators). Some tissues show a response intermediate between ?A and ?2-receptors, which may be explained by the co-existence of both types of ?-receptor. More recently, the existence of a-receptor subtypes has been recognised, based on the development of selective agents.3 Alphai-receptors are the classical post-synaptic a-receptors which mediate smooth muscle contraction, whereas a2-receptors, located presynaptically, reduce the amount of noradrenaline released from the nerve ending?that is, an autoinhibitory effect. There is some evidence that a2-receptors may also be located post-synaptically and on platelets. Prazosin is a selective antagonist of aj-receptors and the plant alkaloid yohimbine a selective antagonist of a2-receptors, whereas phento lamine is equipotent at ax and a2-receptors. Clonidine is a more potent agonist at a2 than ax-receptors.