en Pharmacokinetics/Dynamics Pharmacokinetics/Dynamics Experimental research article Experimental research article <div style="text-align: justify;"><span class="fontstyle0"><strong>Introduction:</strong> </span><span class="fontstyle2">&ldquo;Regulator of G protein signaling&rdquo; (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 G&alpha; 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. </span><span class="fontstyle0"><strong>Methods:</strong> </span><span class="fontstyle2">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. </span><strong><span class="fontstyle0">Results: </span></strong><span class="fontstyle2">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. </span><span class="fontstyle0"><strong>Conclusion:</strong> </span><span class="fontstyle2">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 &beta;-adrenoceptormediated atrial contractility, which is much more prominent in diabetes.</span></div> Regulator of G-protein signaling (RGS) proteins, Atrium, Aorta, Diabetes, Isoprenaline 178 187 http://ppj.phypha.ir/browse.php?a_code=A-10-1124-2&slc_lang=en&sid=1 Mohsen Goharinia 3200319475328460030932 3200319475328460030932 No Department of Pharmacology, Fasa University of Medical Sciences, Fasa, Iran Hossein Mirkhani mirkhanh@sums.ac.ir 3200319475328460030933 3200319475328460030933 Yes Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran