Atypical pharmacologies at beta-adrenoceptors.

Beta-Adrenoceptors are one of the most widely studied groups of G-protein-coupled receptors but continue to provide surprises and insights that have general relevance to pharmacology. Atypical pharmacologies have been described for ligands formerly (and still) described as antagonists acting at beta(1)-, beta(2)- and beta(3)-adrenoceptors that involve ligand-directed signalling and possibly allosteric interactions at the receptors. In the article by Ngala et al., in this issue of the Br J Pharmacol, another example of atypical interactions with beta-adrenoceptors is described, this time for agonists. Some of the responses to BRL37344 and clenbuterol can be explained in terms of actions at beta(2)-adrenoceptors, whereas others such as the increased glucose uptake and palmitate oxidation observed with pM concentrations of BRL37344 may involve interactions with other (possibly allosteric) sites. Atypical pharmacologies of ligands acting at beta-adrenoceptors have already indicated new ways in which ligands can interact with G-protein-coupled receptors and these mechanisms are likely to have important consequences for future drug development.