Adenylyl cyclase responsiveness to guanyl nucleotides in the developing rat heart.

Guanyl nucleotides are effective activators of rat heart adenylyl cyclase activity from the earliest age studied, 16 fetal days, through adulthood. Both guanosine triphosphate and guanylyl-imidodiphosphate (GMP-PNP) significantly enhance epinephrine-stimulated adenylyl cyclase activity at all fetal and postnatal ages. The dose-response curves for epinephrine alone, GMP-PNP alone, or for the combination of epinephrine and GMP-PNP are similar for the newborn and adult heart preparations. Our results indicate that the epinephrine-guanyl nucleotide-adenylyl cyclase system is "mature" as a functional unit in the rat heart even prior to birth. The rat heart adenylyl cyclase system shows a dramatic increase in responsiveness to epinephrine and to guanyl nucleotides just before birth, a responsiveness which rapidly falls by 3 days of neonatal life. With increasing age, the absolute guanosine triphosphate or GMP-PNP activated rate rises in parallel with the basal rate of adenylyl cyclase activity in the rat heart. Speculation. The activation of adenylyl cyclalse systems by guanyl nucleotides may be a general feature of fetal as well as of adult tissues. This activation by guanyl nucleotides may magnify tissue hormonal responses at some stages of development.