Regulation of adenylate cyclase activity in hamster adipocytes. Inhibition by prostaglandins, alpha-adrenergic agonists and nicotinic acid.

Abstract

In ghosts of hamster adipocytes, the regulation of adenylate cyclase (ATP: pyrophosphate lyase, cyclizing; EC 4.6.1.1) activity by prostaglandins, α-adrenergic agonists and nicotinic acid was studied. These three classes of antilipolytic agents caused adenylate cyclase inhibition without an apparent lag phase. Maximal inhibitions observed ranged between about 45% (by α-adrenergic agonists) and 60% (by prostaglandins and nicotinic acid). The order of potency for the inhibitory prostaglandins (PG) was PGE1 ≧ PGE2>PGF2α≅PGI2>PGD2>6-keto PGF1α. The IC50 values obtained were about 0.007, 0.06, 0.3 and 1 μM for PGE1, PGF2α, PGD2 and 6-keto PGF1α, respectively. α-Adrenergic agonists, studied in the presence of the β-adrenergic blocking agent, propranolol (30 μM), inhibited the fat cell enzyme with the order of potency (1)-adrenaline > (1)-α-methylnoradrenaline ≅ (1)-noradrenaline > clonidine ≅ tetryzoline > (1)-phenylephrine. The IC50 values obtained for (1)-adrenaline and (1)-noradrenaline were about 3 and 10 μM, respectively. The inhibitory effect of (1)-adrenaline was blocked by the α-adrenergic antagonists with the potency order yohimbine ≅ phentolamine > prazosin. These findings suggest that an α2 of receptors is involved in this catecholamine-induced inhibition. Nicotinic acid (10 μM) reduced adenylate cyclase activity by about 60% with half-maximal effectiveness at about 0.6 μM. The nicotinic acid derivatives, nicotinamide, β-pyridylcarbinol and NAD (up to 100 μM), had no effect on enzyme activity.