Receptors linked to inhibition of adenylate cyclase: additional signaling mechanisms

Many hormones and neurotransmitters attenuate cyclic AMP (cAMP) accumulation in intact cells by virtue of their ability to inhibit adenylate cyclase activity via the GTP‐binding protein denoted as G i . Nonetheless, a number of physiological findings suggest that attenuation of cAMP production is not sufficient to serve as the only signal for eliciting the diverse physiological effects provoked by these various receptor populations. Additional biochemical and electrophysiological changes are known to occur after occupancy of receptors linked to inhibition of adenylate cyclase, including acceleration of Na + /H + exchange, activation of K + conductances, and inhibition of voltage‐sensitive Ca 2+ channels. This review summarizes the current understanding of how these receptors are coupled to their multiple potential effector mechanisms and offers some speculation about the possible interplay between the biochemical and electrophysiological sequels of receptor occupancy. It is hoped that future studies will establish which constellation of possible signaling mechanisms actually brings about changes in metabolic, secretory, or contractile events in different target cells.— L imbird , L. E. Receptors linked to inhibition of adenylate cyclase: additional signaling mechanisms. FASEB J. 2: 2686‐2695; 1988.