title: Characterization of a potentially reversible increase in beta-adrenergic receptors in isolated, neonatal rat cardiac myocytes with impaired energy metabolism.
abstract: Previous studies have reported that the numbers of beta- and alpha-adrenergic receptors increase in ischemic myocardium. In vivo studies have raised questions regarding the mechanisms involved in the adrenergic receptor alterations and the consequences of these alterations. The purpose of this study was to evaluate potential relationships among beta-adrenergic receptor changes, high energy phosphate reduction, and severity of cell injury in cultured neonatal rat myocytes treated with metabolic inhibitors. The potential for reversal of the receptor changes also was addressed. Binding parameters were measured using [125I]iodocyanopindolol. After 4 hours incubation in potassium cyanide and 2-deoxyglucose, there was a 43% increase in beta-adrenergic receptor number, 41% decrease in adenosine triphosphate, and minimal morphological change in myocytes. Twenty-four hours after removal of the inhibitors, myocytes exhibited a return to normal of the receptor number and adenosine triphosphate level. Iodoacetate treatment for up to 3 hours resulted in marked reduction in adenosine triphosphate and increasing severity of cell injury. The number of beta-adrenergic receptors was unchanged at 1.2 hours, increased at 1.5-2 hours, and decreased at 3 hours. Thus: beta-adrenergic receptor density increases during relatively early stages of injury in metabolically impaired myocytes with reduced adenosine triphosphate levels and decreases subsequently, after the myocytes become irreversibly injured; the increased beta-adrenergic receptor density in moderately injured myocytes can be reversed upon removal of the injurious agent and restoration of the cellular adenosine triphosphate level; and changes in catecholamines mediated by an intact nervous system are not required for an increase in beta-adrenergic receptor density in the setting of impaired energy metabolism.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001667:Binding, Competitive; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D020120:Iodocyanopindolol; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D010869:Pindolol; D011190:Potassium Cyanide