rgs4 inhibition and the effects of adrenoceptor and cholinoceptor agonists on isolated left atrium and aorta of normal and diabetic rats

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.