Adrenergic receptors, G proteins, and cell regulation: implications for aging research

Aging is associated with changes, typically blunting, in response to catecholamines and activation of the sympathetic nervous system. These changes are observed in the presence of a substantial increase in circulating catecholamines. Adrenergic receptors with their linkage to guanine nucleotide binding (G) proteins and to effector molecules provide the critical components between catecholamines and tissue response. In this article, I review recent discoveries related to the expansion of size of adrenergic receptor family and G protein superfamily and the possible implication of these discoveries for research in aging. Nine subtypes of adrenergic receptors have been identified (alpha 1A, alpha 1B, alpha 1C, alpha 2A, alpha 2B, alpha 2C, beta 1, beta 2, beta 3), and other subtypes may yet be identified by molecular cloning techniques. The functional role of all of these receptors remains ill-defined. For the heterotrimeric G proteins, at least 16 alpha, 4 beta, and 4 gamma subunits have been identified. The G alpha subunits are unique among G proteins and have been divided into four principal families, termed Gs, G(i), Gq, and G12. G proteins are multifunctional and can link to multiple effectors. Although it is probable that beta-adrenergic receptors preferentially link to Gs, alpha 1-adrenergic receptors to members of the Gq family, and alpha 2-adrenergic receptors to members of the G1 family, many unanswered questions remain as to the determinants of these linkages.(ABSTRACT TRUNCATED AT 250 WORDS)