Preparation of a liver plasma membrane with an adrenalin‐responsive adenylyl cyclase after inhibition of prostaglandin synthesis by indomethacin

Abstract

Sensitivity of liver adenylyl cyclase to glucagon and to a lesser degree to adrenalin was first reported by Murad et al. [l] . In purified liver plasma membrane preparations adenylyl cyclase is mainly sensitive to glucagon as first found by Pohl et al. [2]. Following Bitensky’s observation [3] that adrenalectomy increases the sensitivity of rat liver adenylyl cyclase towards adrenalin, F. Leray [4] demonstrated a weak stimulation of liver plasma membrane adenylyl cyclase by adrenalin. Cyclic AMP antagonist [5] regulates protein kinase and phosphoprotein phosphatase in an opposite way to CAMP. This antagonist inhibits the adrenalinbut not the glucagon-responsive adenylyl cyclase by phosphorylating this enzyme, most likely in a complex reaction event. [7] . This may be one of the reasons why only very poor responsiveness of adenylyl cyclase to adrenalin has been found in liver plasma membrane preparations. Synthesis of this CAMP antagonist can be inhibited by treatment of rats with indomethacin (H. Wasner, in preparation). The present report shows that liver plasma membrane preparations from indomethacin pretreated rats are highly responsive not only to glucagon but also to adrenalin.