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ExtractIsolated heart cells were prepared from animals newly born toThe basal adenylate cyclase activity of the rat heart increases with the age of the animal. By itself, M glucagon activates only adenylate cyclase activity from adult rat hearts. In contrast, M glucagon in the presence of 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, M, activates adenylate cyclase activity by itself at ages of 14 days and older, but to a far lesser degree than in combination with 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 lo-* 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, thk response is barely measurable but the magnitude of the response increases each week. SpeculationThis 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.We have previously shown that glucagon does not stimulate adenylate cyclase activity in neonatal rat heart (5). Furthermore, when administered to the neonatal rat, glucagon neither depletes myocardial glycogen nor stimulates heart rate (5, 18). Myocardial adenylate cyclase from adult rats is responsive to glucagon (5). Since guanine nucleotides have been reported to enhance the responsiveness of some adenylate cyclase systems to certain hoimones, including glucagon (i4), we have examined the effect of the GTP analog, 5'-GMP-PNP on the responsiveness to glucagon of the neonatal rat cardiac adenylate cyclase. We report here that the adenylate cyclase activity in heart cells isolated from 7-day-old rats is responsive to glucagon in the presence of M GMP-PNP. METHODS AND MATERIALSPregnant rats were purchased to provide young rats of known age (19). Female adult and weanling rats were used; younger animals of either sex were used. 21 days of age as previously described (6). Cells were isolated from hearts of adult rats by the technique of Berry et al.(1) using the reagents described in reference (6).Adenylate cyclase activity was determined by the appearance of cyclic

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