RT - Journal Article T1 - RGS4 inhibition and the effects of adrenoceptor and cholinoceptor agonists on isolated left atrium and aorta of normal and diabetic rats JF - Physiol-Pharmacol YR - 2022 JO - Physiol-Pharmacol VO - 26 IS - 2 UR - http://ppj.phypha.ir/article-1-1696-en.html SP - 178 EP - 187 K1 - Regulator of G-protein signaling (RGS) proteins K1 - Atrium K1 - Aorta K1 - Diabetes K1 - Isoprenaline AB - 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 was treated with increasing concentrations of phenylephrine and acetylcholine. Isolated left atrium was 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-adrenoceptormediated atrial contractility, which is much more prominent in diabetes. LA eng UL http://ppj.phypha.ir/article-1-1696-en.html M3 10.52547/phypha.26.2.4 ER -