Demonstration of Dopamine-sensitive Adenylate Cyclase in Malignant Neuroblastoma Cells and Change in Sensitivity of Adenylate Cyclase to Catecholamines in “Differentiated” Cells*

AUTOR(ES)

Prasad, Kedar N.

RESUMO

Adenylate cyclase (EC 4.6.1.1) activity was stimulated by low concentrations of dopamine and apomorphine, but not by low concentrations of norepinephrine in homogenates of malignant mouse neuroblastoma cells. In cyclic AMP-induced “differentiated” cells, dopamine concentration required for a maximal increase in adenylate cyclase activity was about 10-fold less than that required for a similar increase in control cells, and norepinephrine-sensitive adenylate cyclase activity became apparent at low norepinephrine concentrations. The pharmacological properties of dopamine-sensitive adenylate cyclase were different from those of norepinephrine-sensitive enzyme. For example, dopamine-stimulated adenylate cyclase activity was markedly reduced by low concentrations of haloperidol and phentolamine, whereas norepinephrine-stimulated enzyme activity required higher concentrations of these blocking agents for a similar amount of inhibition. Norepinephrine-stimulated enzyme activity was markedly blocked by low concentrations of propranolol, whereas dopamine-stimulated enzyme activity required a much higher concentration of this blocking agent for a similar amount of inhibition. Low concentrations of isoproterenol increased adenylate cyclase activity in malignant cells, but in “differentiated” cells even a high concentration failed to do so. The fact that dopamine and norepinephrine produced an additive stimulatory effect on adenylate cyclase activity suggests that they interact at different receptor sites. This suggestion is further supported by the observation that the combination of prostaglandin E1 and norepinephrine produced an additive stimulatory effect of enzyme activity. The observation that the effects of dopamine and prostaglandin E1 are not additive, coupled with the observation that a low concentration of phentolamine blocked the effect of prostaglandin E1, suggests that these two agents may interact at a common site.

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