Possible existence of two mechanisms involved in alpha 1-adrenergic action: effect of Sgd 101/75

The effect of 2-(2-methyl-indazol-4-imino)-imidazoline (Sgd 101/75) on the rate of urea synthesis by isolated rat hepatocytes was studied. This agent was observed to stimulate ureagenesis through the activation of alpha 1-adrenoceptors (prazosin-sensitive). The effect of Sgd 101/75 was dependent on the presence of calcium and was not affected by insulin. The active phorbol ester, phorbol 12-myristate 13-acetate, blocked the effect of Sgd 101/75. It was also observed that this adrenoceptor agonist was unable to stimulate ureagenesis in hepatocytes obtained from hypothyroid rats but produced clear stimulation of this metabolic pathway in cells obtained from adrenalectomized rats. The data indicate that this agonist stimulates hepatic metabolism through a calcium-dependent, insulin-insensitive pathway for alpha 1-adrenergic action, modulated by the thyroid status of the animal.