Dose-dependent influence of buprenorphine on the phospholipid composition of cat hepatocyte plasma membranes in hemorrhagic shock

Abstract

It is established that buprenorphine (0.3 mg/kg) induces considerable alterations in the phosphohpid composition of hepatocyte plasma membranes as a result of phosphatidylserine accumulation and a considerable loss of sphingomyelin and lysophosphatidylserine. When administered in a dose of 0.03 mg/kg, buprenorphine facilitates normalization of the phosphoinositol turnover in hepatocyte plasma membranes.Endogenous opioid peptides are known to be a factor in the pathogenesis of shock. They cause marked venodilation, thus cutting off a considerable volume of blood from the central and peripheral circulation. It is known that antagonists of opiate receptors improve the function of the cardiovascular system during shock [6]. However, in some cases naloxone has no effect on this system and on the survival of animals [16]. On the other hand, by reducing opiate analgesia, naloxone can sometimes induce lethal changes in the function of the cardiovascular system [5]. Different results have been obtained in clinical studies of the consequences of naloxone administration during shock [3,12]. At the same time, it has been reported that in various models of shock agortists and antagonists of opioid peptides ehcit a protective effect on hemodynamics [4]. Administration of these preparations during shock resulted in analgesia with improvement of cardiovascular function. Buprenorphine (BPN) is one of these preparations [4]. In this Laboratory o[ Pathophysiology of Shock, Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow. (Presented by G. N. Kryzhanovskii, Member of the Russian Academy oI Medical Sciences)study we examined the effect of BPN on the phospholipid composition of hepatocyte plasma membranes in hemorrhagic shock. This is of interest because BPN is a highly hpophilic compound and rapidly dissolves in the cell membrane hpids [9], owing to which it can directly influence the lipid component of the plasma membrane. MATERIALS AND METHODSExperiments were performed on 24 cats (3+0.5 kg) under ethanol-sodium anesthesia (40 mg/kg intraperitoneally). Hemorrhagic shock was performed by the method of Wiggers-Fine. Blood coagulation in the catheters was prevented by administration of 2000 U/kg heparin (HP). Thirty minutes after HP administration, blood was drained to attain a blood pressure of 40 mm Hg, and this pressure was maintained during a 1-h time period. The effect of BPN (0.03 and 0.3 mg/kg) was studied against the background of hemorrhagic shock. Intact animals treated with the same dose of BPN served as controls. The material for investigation was collected 2 h after anesthesia. After isolation of hepatocyte plasma membranes [1] and after extraction of total lipids [14], phospholipids were fractionated