GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens |
| |
| Institution: | 1. Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, SP, Brazil;2. Inst. of Chemistry – São Paulo State University- UNESP, 14801-970 Araraquara, SP, Brazil;3. Department of Morphology, Dental School at Araraquara, Univ. Estadual Paulista – UNESP, Araraquara, SP, Brazil;3. Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200 and;4. the Departments of Medicine, Pharmacology, and Toxicology, Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202;1. Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China;2. Shannxi Provincial Key Laboratory of Gastrointestinal Motility Disorders, Xi’an 710004, China;3. Shannxi Provincial Clinical Research Center of Gastrointestinal Diseases, Xi’an 710004, China;3. Research Service, Veterans Affairs Medical Center, Denver, Colorado 80220;4. Department of Biological Sciences and Eleanor Roosevelt Institute, University of Denver, Denver, Colorado 80208;5. Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany, and;6. Division of Clinical Pharmacology and Toxicology, Department of Medicine and Neuroscience Program, University of Colorado Denver, Aurora, Colorado 80045;3. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232;4. Department of Biological Sciences, Vanderbilt University College of Arts and Sciences, Nashville, Tennessee 37232 |
| |
| Abstract: | The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which release NE on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release Epi (mainly) and NE. All of the Epi in the body and a significant amount of circulating NE derive from the adrenal medulla. The secretion of CAs from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors, the vast majority of which are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as “presynaptic autoreceptors” in this regard. There is a plethora of CA-secretagogue signals acting on these receptors but some of them, most notably the α2ARs, inhibit CA secretion. Over the past few years, however, a few new proteins present in chromaffin cells have been uncovered to participate in CA secretion regulation. Most prominent among these are GRK2 and β-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function. The present review will discuss the molecular and signaling mechanisms by which adrenal chromaffin cell-residing GPCRs and their regulatory proteins modulate CA synthesis and secretion. Particular emphasis will be given to the newly discovered roles of GRK2 and β-arrestins in these processes and particular points of focus for future research will be highlighted, as well. |
| |
| Keywords: | β-Arrestin Catecholamine secretion Chromaffin cell GPCR GRK2 Signal transduction |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
