Cardiac 7-transmembrane-spanning domain receptor portfolios: diversify, diversify, diversify

Enhanced signaling in myocytes by the G protein G(q) has been implicated in cardiac hypertrophy and the transition to heart failure. alpha(1)-Adrenergic receptors (alpha(1)-Alts) are members of the 7-transmembrane-spanning domain (7-TM) receptor family and signal via interaction with G(q) in the heart. The specific effects of a loss of alpha(1)-AR signaling in the heart are explored by O'Connell et al. in this issue of the JCI (see the related article beginning on page 1005). Paradoxically, gene ablation of the alpha(1A) and alpha(1 beta) subtypes in mice results in a maladaptive form of reactive cardiac hypertrophy from pressure overload, with a predisposition to heart failure. Thus signaling to the alpha(1)-AR (compared with signaling from other receptors such as angiotensin receptors, which also couple to G(q)) appears to be specifically required for a normal hypertrophic response. This represents another example of how receptors that share common G proteins have diversified, developing unique signaling programs. These findings may have particular clinical relevance because of the widespread use of alpha(1)-AR antagonists in the treatment of hypertension and symptomatic prostate enlargement.