Development of Guanylylimidodiphosphate-dependent Activation of Adenylate Cyclase by Glucagon in the Neonatal Rat Heart

Abstract

Extract: The basal adenylate cyclase activity of the rat heart increases with the age of the animal. By itself, 10⁻⁵ M glucagon activates only adenylate cyclase activity from adult rat hearts. In contrast, 10⁻⁵ M glucagon in the presence of 10⁻⁴ M 5'-guanylylimidodiphosphate (GMP-PNP) clearly activates adenylate cyclase activity in the 14-day-old rat heart, with some activation being evident in hearts of 7-day-old animals. GMP-PNP, 10⁻⁴ M, activates adenylate cyclase activity by itself at ages of 14 days and older, but to a far lesser degree than in combination with 10⁻⁵ M glucagon. Activity elicited by NaF increases throughout the neonatal period. The ratio of NaF-stimulated activity to basal activity increases from 6.3 at 2 days to 10.0 in the adult, a change which is not statistically significant. We conclude that a cardiac receptor for glucagon is present early in neonatal period of the rat, but this receptor cannot effect activation of adenylate cyclase and an increase in heart rate, or depletion of glycogen. Even in the presence of 10⁻⁴ GMP-PNP, the response to glucagon by cardiac adenylate cyclase depends on the age of the rat. In heart cells from a 7-day-old rat, the response is barely measurable but the magnitude of the response increases each week. Speculation: This study demonstrates that GMP-PNP, an analog of GTP, facilitates the activation of adenylate cyclase by glucagon in the neonatal rat heart. It remains to be determined whether GMP-PNP facilitates glucagon binding per se or the interaction of glucagon with adenylate clyclase. The effect of the naturally occurring GTP on newborn cardiac adenylate cyclase activity is unknown.