Regulation of Cardiac beta(3)-Adrenergic Receptors in Hyperglycemia


Turan B., TUNCAY E.

INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS, vol.51, no.6, pp.483-492, 2014 (Peer-Reviewed Journal) identifier

  • Publication Type: Article / Article
  • Volume: 51 Issue: 6
  • Publication Date: 2014
  • Journal Name: INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.483-492
  • Keywords: beta-Blockers, beta-Adrenoceptor subtypes, Heart function, Oxidative stress, Diabetes mellitus, BETA-ADRENERGIC-RECEPTORS, ALTERED CONTRACTILE RESPONSE, NITRIC-OXIDE SYNTHASE, RAT-HEART, DIABETIC CARDIOMYOPATHY, CARDIOVASCULAR-DISEASE, INTRACELLULAR CA2+, OXIDATIVE STRESS, CALCIUM-RELEASE, UP-REGULATION

Abstract

Beta-adrenoceptors (beta-AR), members of the G protein-coupled receptors play important roles in the regulation of heart function. A positive inotropic action of catecholamines is mediated through their interaction with beta-AR, located on the sarcolemma, while they can also mediate some deleterious effects, such as cardiac arrhythmias or myocardial apoptosis. The well-known beta-AR-associated signaling in heart is composed of a coupled mechanism among both beta(1)- and beta(2)-AR and stimulatory G protein (G(s)). This coupled mechanism further leads to the activation of adenylyl cyclase and thereby increases in intracellular cAMP level. However, recent studies have emphasized the contribution of constitutive beta(3)-AR coupling to G(i) proteins, thereby initiating additional signal transduction pathways, particularly under physiopathological conditions. Diabetic cardiomyopathy, as a distinct entity is recognized due to its diminished responsiveness to beta(1)-AR agonist stimulation in the heart from diabetic rats with no important changes in the responses mediated with beta(2)-AR. Furthermore, an upregulation of beta(3)-AR has been shown in diabetic rat heart with a strong negative inotropic effect on left ventricular function. Experimental data provide evidences that the mechanisms for the negative inotropic effect with beta(3)-AR activation appear to involve a pertussis toxin (PTX)-sensitive G protein and the activation of a nitric oxide synthase pathway. On the other hand, beta-blockers demonstrate marked beneficial effects in heart dysfunction with scavenging free radicals and/or acting as an antioxidant with both sex- and dose-dependent manner. However, further investigations are needed to clarify the roles of both altered expression and/or responsiveness of beta-AR and the benefits with beta-blocker treatment in diabetes. This review discusses the role of beta-AR activation, particularly beta(3)-AR in cardiac pathological remodeling under hyperglycemia.