J.F. Mackenzie

Importance of Agonists in α-Adrenoceptor Classification and Localisation of α1-Adrenoceptors in Human Prostate

α-Adrenoceptor blocker drugs are commonly used in the clinical (non-surgical) treatment of BPH. α1-adrenoceptors were originally sub-divided using agonists but, subsequently, were sub-divided using only antagonists in ligand-ligand interactions, which did not require agonists at all. Ultimately, proof that adrenoceptors are functional receptors for the natural ligands, noradrenaline and adrenaline, requires that agonists be used. The earlier excitement engendered by finding varying agonist potency series in different tissues has not been revisited to place it in the context of current concepts of α1-adrenoceptor subtypes. This review will consider the advantages and limitations of different agonists for the study of α1-adrenoceptor subtypes including ‘extreme’ examples where the archetypal α1-adrenoceptor agonist phenylephrine activates α2-adrenoceptors and others where UK14304, often the α2-adrenoceptor agonist of choice, activates α1-adrenoceptors. New work will also be presented showing the interaction between agonists and the fluorescent α1-adrenoceptor antagonist QAPB. This introduces the novel point of view of studying the displacement of antagonists by agonists. Possible errors in antagonist classification arising from complexity in the actions of agonists and the recently developed method of fluorescent ligand binding on isolated living human prostatic smooth muscle cells will be discussed.