Effect of trifluoperazine on the stimulation by Ca2+-dependent hormones of gluconeogenesis from glutamine in isolated hepatocytes.

In continuation of our previous studies we have investigated some aspects of the hormonal control of glutamine metabolism in isolated rat hepatocytes. (1)Catecholamines, angiotensin II and vasopressin stimulate gluconeogenesis from glutamine more than 2-fold. These effects require the presence of Ca2+ in the incubation medium. (2) The phenothiazine, trifluoperazine, a purported specific inhibitor of calmodulin, completely blocks the stimulation by catecholamines without affecting the response to the other two hormones. (3) The effectiveness of trifluoperazine in preventing the stimulation of gluconeogenesis by catecholamines was dependent on the concentrations of both the hormones and the inhibitor. (4) Trifluoperazine, at concentrations that prevent stimulation by epinephrine of gluconeogenesis, was as effective as phentolamine in blocking the binding of [3H]epinephrine to intact hepatocytes. (5) These studies support the view (Blackmore, P.F., El-Refai, M.F., Dehaye, J.-P., Strickland, W.G., Haghes, B.P. and Exton, J.H. (1981) FEBS Lett. 123, 245--248) that inhibition by trifluoperazine of alpha-adrenergic stimuli does not necessarily mean that calmodulin is involved in post-receptor events.