Lack of desensitization against alpha-agonists and vasopressin in the liver.

A heterologous and homologous desensitization of the glycogenolytic response against 3',5'-cAMP independent hormones in isolated hepatocytes has been reported [Biochem. J. (1981) 200, 509-514]. We re-examined this phenomenon in isolated perfused rat livers, isolated hepatocytes during stationary incubation and in isolated perifused hepatocytes. The release of glucose and the activation of glycogen phosphorylase were followed in the presence of phenylephrine (10(-5) M) or vasopressin (2.5 X 10(-8) M). A desensitization against these hormones could not be observed in the presence of exogenous calcium (1.3 mM). When calcium-free media were applied, the perfused liver became successively resistant toward the action of phenylephrine (or vasopressin), but regained sensitivity immediately after addition of 1.3 mM calcium to the medium. It is concluded that in isolated hepatocytes desensitization against hormones acting via mobilization of intracellular calcium is an artifact resulting from the experimental conditions.