Editing Chromaffin cell (section)

=== Heart failure ===
Following [[heart failure]], the body increases sympathetic activity to the adrenal medulla as the compensatory mechanism to increase heart rate and [[cardiac output]]. This increased sympathetic activity leads to chronically increased synthesis and secretion of catecholamines from the adrenal chromaffin cells. This chronic increase of epinephrine and norepinephrine secretion causes desensitization of the chromaffin cells to catecholamines resulting in a decrease in production and presence of α<sub>2</sub> adrenergic receptors on their cell membrane. This desensitization and downregulation of [[Adrenergic receptor|α<sub>2</sub> adrenergic]] receptors is caused by the upregulation of the enzyme Adrenal G protein coupled receptor kinase 2 ([[Beta adrenergic receptor kinase|GRK2]]) which effectively eliminates the normal autocrine-type [[negative feedback]] that normally prevents the cells from over producing the catecholamines and replaces it with a positive feedback loop in which increased secretion further elicits more secretion.<ref>{{Cite journal|last1=Jafferjee|first1=Malika|last2=Reyes Valero|first2=Thairy|last3=Marrero|first3=Christine|last4=McCrink|first4=Katie A.|last5=Brill|first5=Ava|last6=Lymperopoulos|first6=Anastasios|date=2016-03-01|title=GRK2 Up-Regulation Creates a Positive Feedback Loop for Catecholamine Production in Chromaffin Cells|journal=Molecular Endocrinology|volume=30|issue=3|pages=372–381|doi=10.1210/me.2015-1305|issn=0888-8809|pmc=5414648|pmid=26849467}}</ref> This upregulation of GRK2 is also accompanied by upregulation and increased production of the enzyme [[tyrosine hydroxylase]], which catalyzes the rate limiting step of catecholamine synthesis.<ref>{{Cite journal|last1=Lymperopoulos|first1=Anastasios|last2=Rengo|first2=Giuseppe|last3=Gao|first3=Erhe|last4=Ebert|first4=Steven N.|last5=Dorn|first5=Gerald W.|last6=Koch|first6=Walter J.|date=2010-05-21|title=Reduction of Sympathetic Activity via Adrenal-targeted GRK2 Gene Deletion Attenuates Heart Failure Progression and Improves Cardiac Function after Myocardial Infarction|journal=Journal of Biological Chemistry|language=en|volume=285|issue=21|pages=16378–16386|doi=10.1074/jbc.M109.077859|issn=0021-9258|pmc=2871505|pmid=20351116|doi-access=free}}</ref>