IMPAIRED PROTEIN-KINASE-C ACTIVATION IS ASSOCIATED WITH DECREASED HEPATIC ALPHA(1)-ADRENOCEPTOR RESPONSIVENESS IN ADRENALECTOMIZED RATS

The present work aimed to study the influence of corticosteroids on th e alpha(1)-adrenoreceptor-induced activation of hepatic metabolic func tions. The experiments were performed in a nonrecirculating liver perf usion system featuring continuous monitoring of pO(2), pCa(2+), Ca2+, pH, and portal pressure. The alpha(1)-adrenergic-induced stimulation o f respiration, H+ and Ca2+ release, glycogen breakdown, and gluconeoge nesis, were diminished in livers from adrenalectomized animals. The no rmal liver responsiveness was restored on administration of exogenous corticosteroids but not mineralocorticoids. The following observations support the conclusion that corticosteroids control a hepatocyte-spec ific early postreceptor step in the alpha 1-adrenergic signaling pathw ay: 1) the alpha(1)-adrenergic stimulation of vascular smooth muscle c ontraction was not impaired by corticosteroid deficiency; 2) the alpha (1)-adrenoreceptor ligand-binding affinity does not seem to be altered by adrenalectomy; 3) the alpha(1)-adrenergic-induced intracellular al kalosis, protein kinase C activation, and Ca2+ mobilization were dimin ished in hepatocytes from adrenalectomized rats, indicating that both Ca2+-dependent and -independent processes were altered; and 4) non-rec eptor-mediated homeostatic mechanisms of metabolic or intracellular pH control were not impaired by adrenalectomy.