REGULATION OF UTERINE SMOOTH-MUSCLE CELL BETA-ADRENERGIC CATECHOLAMINE-SENSITIVE ADENYLATE-CYCLASE BY MG2+ AND GUANYLYL NUCLEOTIDE

The β-adrenergic catecholamine agonist, isoproterenol, and the guanylyl nucleotide, GTP, had synergistic effects in elevating adenylate cyclase activity in uterine smooth muscle cell homogenates. The guanylyl nucleotide-dependent step included an increase in enzyme sensitivity to Mg2+. The Mg2+ requirements of the enzyme were independent of the ATP-substrate concentration, and the guanylyl nucleotidedependent activation step did not require either the divalent cation or enzymatic activity. These properties are most consistent with a two-stage enzyme model in which the equilibrium between Mg2+-sensitive and insensitive forms is modulated by guanylyl nucleotide. The activated enzyme state was transient and reversible, but reversion to the basal state probably required hydrolysis of GTP. Guanylyl nucleotide regulation extended to the interaction of isoproterenol with the smooth muscle cell β-adrenergic catecholamine receptor, but this effect was probably separate from the enzyme activation step. © 1979.