Possible involvement of two mechanisms of signal transduction in α1-adrenergic action. Selective effect of cycloheximide

Abstract

We have previously suggested that the effects of α 1-adrenergic agents on hepatocyte metabolism involve two pathways: (a) a calcium-independent, insulin-sensitive process which is modulated by glucocorticoids; and (b) a calcium-dependent, insulin-insensitive process which is modulated by thyroid hormones. Cycloheximide stimulated ureogenesis through a prazosin-sensitive mechanism in liver cells ( α 1-adrenergic). The effect of cycloheximide was insulin-insensitive and calcium-dependent. Furthermore, a clear effect of cycloheximide was observed in hepatocytes obtained from adrenalectomized animals, whereas no effect was observed in cell from hypothyroid rats. The effects of epinephrine and cycloheximide were blocked by phorbol esters in all the conditions tested. Binding competition experiments indicated that cycloheximide interacts with only a fraction of the α 1-adrenergic sites labeled with [ 3H]prazosin. It is suggested that cycloheximide activates preferentially one of the pathways involved in the α 1-adrenergic action in liver cells.