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Abstract:   (281 Views)
Introduction: “Regulator of G protein signaling” (RGS) proteins are a family of various proteins that are expressed in different tissues and accelerate hydrolysis rate of GTP to GDP by several thousand-fold increase in GTPase activity of Gα subunit. Thus, they act as negative regulators of G protein-coupled receptors (GPCRs) signaling. In this study, the effect of CCG-50014, a RGS4 inhibitor, on isolated aorta and left atrium of normal and diabetic rats has been investigated.
Methods: Isolated aorta were treated with increasing concentrations of phenylephrine, acetylcholine; and isolated left atrium were treated with increasing concentrations of acetylcholine and isoprenaline, both in the absence and presence of CCG-50014. The pEC50 (negative logarithm of the concentration which produces half maximal response) and maximum response of each compound were extracted from concentration-response curves.
Results: Pre-treatment of aorta with CCG-50014 had no important effect on the response to phenylephrine and acetylcholine. CCG-50014 decreased isoprenaline inotropic potency on normal atrium but had no effect on its maximum response. In diabetic atrium, CCG-50014 dramatically reduced both the pEC50 and maximum response of isoprenaline. CCG-50014 did not affect normal atrium response to acetylcholine but in diabetic atrium, it caused a small yet significant decrease in the pEC50 of acetylcholine while increased its maximum relaxing effect.
Conclusion: It seems that RGS4 is not involved in the termination of GPCRs signaling in rat aorta. In atrium, RGS4 inhibition unexpectedly results in attenuation of β-adrenoceptor-mediated atrial contractility which is much more prominent in diabetes.
Types of Manuscript: Original Research | Subject: Pharmacology

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