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Alpha 1-adrenoceptors: function and phosphorylation.
J A García-Sáinz1, J Vázquez-Prado, L del Carmen Medina
1Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. Apartado postal 70-248, México, Mexico. agarcia@ifisiol.unam.mx
European Journal of Pharmacology
|February 25, 2000
Summary
Alpha(1)-adrenoceptor phosphorylation by kinases causes receptor desensitization and internalization. This process, involving G protein-receptor kinases and protein kinase C, is crucial for receptor regulation.
Area of Science:
- Pharmacology
- Cellular Biology
- Molecular Biology
Background:
- Alpha(1)-adrenoceptors mediate various physiological responses.
- Agonist stimulation leads to homologous desensitization of alpha(1B)-adrenoceptors.
- Receptor desensitization is linked to phosphorylation events.
Purpose of the Study:
- To review the phosphorylation and function of alpha(1)-adrenoceptors.
- To elucidate the kinases and sites involved in alpha(1B)-adrenoceptor regulation.
- To understand the role of receptor phosphorylation in desensitization and internalization.
Main Methods:
- Review of existing literature on alpha(1)-adrenoceptor signaling.
- Analysis of studies on hamster alpha(1B)-adrenoceptor phosphorylation.
- Identification of kinase involvement and phosphorylation sites.
Main Results:
- Agonist stimulation causes homologous desensitization via G protein-receptor kinase-mediated phosphorylation at Ser(404), Ser(408), and Ser(410).
- Protein kinase C activation leads to desensitization/internalization through phosphorylation at Ser(394) and Ser(400).
- Heterologous desensitization involves protein kinase C, tyrosine kinase, and phosphatidyl inositol 3-kinase, highlighting their pivotal roles.
Conclusions:
- Receptor phosphorylation is a key mechanism for alpha(1)-adrenoceptor desensitization and internalization.
- Multiple kinase pathways, including G protein-receptor kinases, protein kinase C, and others, regulate alpha(1)-adrenoceptor function.
- Understanding these phosphorylation events is critical for comprehending adrenoceptor regulation.