alpha(1)-adrenoceptors: function and phosphorylation

This review focuses on alpha(1)-adrenoceptor phosphorylation and function. Most of what is currently known is based on studies on the hamster alpha(1B )-adrenoceptor. It is known that agonist stimulation leads to homologous de sensitization of these receptors and current evidence indicates that such d ecrease in receptor activity is associated with receptor phosphorylation. S uch receptor phosphorylation seems to involve G protein-receptor kinases an d the receptor phosphorylation sites have been located in the carboxyl tail (Ser(404), Ser(408) and Ser(410)). There is also evidence showing that in addition to desensitization, receptor phosphorylation is associated with in ternalization and roles of beta-arrestins have been observed. Direct activa tion of protein kinase C leads to receptor desensitization/internalization associated with phosphorylation; the protein-kinase-C-catalyzed receptor ph osphorylation sites have been also located in the carboxyl tail (Ser(394) a nd Ser(400)). Activation of G(q)-coupled receptors, such as the endothelin ETA receptor induces alpha(1B)-adrenoceptor phosphorylation and desensitiza tion. Such effect involves protein kinase C and a yet unidentified tyrosine kinase. Activation of Gi-coupled receptors, such as the lysophosphatidic a cid receptor, also induces alpha(1B)-adrenoceptor phosphorylation and desen sitization. These effects involve protein kinase C and phosphatidyl inosito l 3-kinase. Interestingly, activation of epidermal growth factor receptors also induces alpha(1B)-adrenoceptor phosphorylation and desensitization inv olving protein kinase C and phosphatidyl inositol 3-kinase. A pivotal role of these kinases in heterologous desensitization is evidenced. (C) 2000 Els evier Science B.V. All rights reserved.