125I-Glucagon Binding and Adenylate Cyclase Activation in the Fetal Rat Heart

Abstract

The polypeptide hormone, glucagon, initiates a number of physiological responses including glycogenolysis, lipolysis, insulin release, and increases in heart rate and myocardial contractility. The actions, like those of many other hormones on their respective target tissues, are thought to be mediated by the activation of the membrane-bound enzyme, adenylate cyclase and the resultant increase in the intracellular concentration of adenosine 3 ', 5 '-monophosphate (cyclic AMP). Following the classic description of the glucagon and epinephrine mediated increases in hepatic cyclic AMP by Sutherland and Rall( 1) and the delineation of cyclic AMP as the mediator of the action of these hormones on glycogenolysis, Sutherland and his coworkers proposed four criteria which should be fulfilled before concluding that the effects of a hormone on its target organ were mediated by cyclic AMP ( 2 ) . These criteria have been fulfilled for the actions of glucagon on the heart. One, glucagon activates adenylate cyclase in broken cell preparations of myocardium (3, 4). Two, glucagon increases cyclic AMP levels in intact, isolated perfused hearts ( 5 ) . Three, the inotropic effects of glucagon are potentiated by the phosphodiesterase inhibitor, theophylline (6). Four, the dibutyryl derivative of cyclic AMP has a positive inotropic effect on heart muscle similar to that of glucagon ( 7 , 8).

Responsiveness to glucagon in fetal hearts. Species variability and apparent disparities between changes in beating, adenylate cyclase activation, and cyclic AMP concentration.

“…DISCUSSION The data obtained in this study demonstrate that the appearance of cardiac responsiveness to glucagon occurs at around 17-18 days' gestational age in the mouse fetus, well before term. In contrast, as suggested previously by Clark et al (5), functional maturation of cardiac responsiveness to glucagon in the rat appears not to occur until after birth, although some laboratories have reported binding of glucagon and activation of adenylate cyclase in homogenates of fetal rat hearts (12). Previous studies from other laboratories have suggested that hearts of lambs, like those of rats, fail to respond functionally to glucagon in the fetal and newborn period (3,4).…”