Regulation of cardiac β3-adrenergic receptors in hyperglycemia


TURAN B., TUNCAY E.

Indian Journal of Biochemistry and Biophysics, cilt.51, sa.6, ss.483-492, 2014 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 51 Sayı: 6
  • Basım Tarihi: 2014
  • Dergi Adı: Indian Journal of Biochemistry and Biophysics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.483-492
  • Anahtar Kelimeler: Blockers, Diabetes mellitus, Heart function, Oxidative stress, β-Adrenoceptor subtypes
  • Lokman Hekim Üniversitesi Adresli: Hayır

Özet

© 2014, National Institute of Science Communication and Information Resources (NISCAIR). All rights reserved.Beta-adrenoceptors (β-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 β-AR, located on the sarcolemma, while they can also mediate some deleterious effects, such as cardiac arrhythmias or myocardial apoptosis. The well-known β-AR-associated signaling in heart is composed of a coupled mechanism among both β1- and β2-AR and stimulatory G protein (Gs). 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 β3-AR coupling to Gi 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 β1-AR agonist stimulation in the heart from diabetic rats with no important changes in the responses mediated with β2-AR. Furthermore, an upregulation of β3-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 β3-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, β-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 β-AR and the benefits with β-blocker treatment in diabetes. This review discusses the role of β-AR activation, particularly β3-AR in cardiac pathological remodeling under hyperglycemia.