Human fat cell adenylate cyclase. Modulation of parathyroid hormone action by guanine nucleotides

The effects of guanine nucleotides on basal and parathyroid hormone-stimulated adenylate cyclase of human fat cell ghosts were studied. GTP (10(-7)-10(-3) M) caused a dose-dependent inhibition of basal enzyme activity, but it had no significant effect on PTH-stimulated rates of cAMP-formation. The guanine nucleotide analogue 5'-guanylyl-imidodiphosphate GMP (PNP) when applied in the same concentration range, stimulated basal as well as PTH-activated adenylate cyclase activity up to 300%. GMP (PNP) activation was non-linear with time. PTH-activated the human fat cell adenylate cyclase via an individual receptor distinct from beta-adrenergic receptor sites.