Characterization of lymphocyte beta 2-adrenoceptor signalling in patients with left ventricular volume overload disease

Clinical and Experimental Pharmacology & Physiology
N DzimiriZohair Al-Halees

Abstract

1. Studies using animal experimental models have suggested that the beta2-adrenoceptor is uncoupled in association with alterations in the expression of G-protein-coupled receptor kinases (GRK) 2/3 in heart failure. However, the functional expression of the components of this pathway in human disease has not been fully elucidated yet. In the present study, we evaluated the possibility that the regulation of beta2-adrenoceptor signalling components in patients with left ventricular volume overload (VOL) depends on the severity of the overload. 2. We characterized the lymphocyte GRK 2-6, beta-arrestins 1 and 2, beta2-adrenoceptor expression at the mRNA and protein levels, as well as the activity of adenylyl cyclase, protein kinases (PK) A and PKC in patients with VOL using healthy blood donors as controls. 3. In the patient group, GRK2 mRNA was increased by 61% (P < 0.001), GRK3 was increased by 54% (P < 0.005), GRK5 was increased fivefold (P < 0.001) and the beta-arrestin 2 mRNA was increased by 40% (P < 0.05). These increases were paralleled with a sixfold increase in GRK2, a twofold increase in GRK3 and a 1.3-fold increase in GRK5 protein levels. These changes were associated with a significant decrease in beta2-adrenoceptor m...Continue Reading

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Citations

May 17, 2005·Cellular Signalling·Thierry MétayéJean-Louis Kraimps
Sep 23, 2003·Cellular Signalling·Petronila PenelaFederico Mayor
Jan 30, 2004·Fundamental & Clinical Pharmacology·Nduna DzimiriZohair Al-Halees
Dec 15, 2015·Frontiers in Cardiovascular Medicine·Gabriele Giacomo SchiattarellaGiovanni Esposito
May 18, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jonathan HullmannWalter J Koch
Jan 8, 2009·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·N ChettyH R Irving
Nov 24, 2017·American Journal of Physiology. Cell Physiology·Gleisy Kelly GoncalvesAdelina M Reis
Dec 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katia VaraniMaria P Abbracchio
Oct 2, 2002·European Journal of Biochemistry·Nduna Dzimiri
Jun 12, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Fermí MontóPilar D'Ocon
Mar 7, 2021·International Journal of Molecular Sciences·Federica MarzanoAlessandro Cannavo

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