Mechanisms involved in α 1B ‐adrenoceptor desensitization

α 1B ‐Adrenergic receptors mediate many of the actions of the natural catecholamines, adrenaline and noradrenaline. They belong to the seven transmembrane domains G protein‐coupled receptor superfamily and exert their actions mainly through activation of Gq proteins and phosphoinositide turnover/calcium signaling. Many hormones and neurotransmitters are capable of inducing α 1B ‐adrenergic receptor phosphorylation and desensitization; among them: adrenaline and noradrenaline, phorbol esters, endothelin‐I, bradykinin, lysophosphatidic acid, insulin, EGF, PDGF, IGF‐I, TGF‐β, and estrogens. Key protein kinases for these effects are G protein coupled receptor kinases and protein kinase C. The lipid/protein kinase, phosphoinositide‐3 kinase also appears to play a key role, acting upstream of protein kinase C. In addition to the agents employed for cells stimulation, we observed that paracrine/autocrine mediators also participate; these processes include EGF transactivation and sphingosine‐1‐phosphate production and action. The complex regulation of these receptors unlocks opportunities for therapeutic intervention. © 2011 IUBMB IUBMB Life, 2011