Impaired protein kinase C activation is associated with decreased hepatic alpha 1-adrenoreceptor responsiveness in adrenalectomized rats.
The present work aimed to study the influence of corticosteroids on the alpha 1-adrenoreceptor-induced activation of hepatic metabolic functions. The experiments were performed in a nonrecirculating liver perfusion system featuring continuous monitoring of pO2, pCa2+, Ca2+, pH, and portal pressure. The alpha 1-adrenergic-induced stimulation of respiration, H+ and Ca2+ release, glycogen breakdown, and gluconeogenesis, were diminished in livers from adrenalectomized animals. The normal liver responsiveness was restored on administration of exogenous corticosteroids but not mineralocorticoids. The following observations support the conclusion that corticosteroids control a hepatocyte-specific early postreceptor step in the alpha 1-adrenergic signaling pathway: 1) the alpha 1-adrenergic stimulation of vascular smooth muscle contraction 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 alkalosis, protein kinase C activation, and Ca2+ mobilization were diminished in hepatocytes from adrenalectomized rats, indicating that both Ca(2+)-dependent and -independent processes were altered; and 4) non-receptor-mediated homeostatic mechanisms of metabolic or intracellular pH control were not impaired by adrenalectomy.
Department of Physiopathology and Human Molecular Genetics, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
G
G
Ciprés
N
N
Butta
E
E
Urcelay
R
R
Parrilla
A
A
Martin-Requero
D000305:Adrenal Cortex Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D018340:Receptors, Adrenergic, alpha-1; D014667:Vasopressins; D011493:Protein Kinase C; D002118:Calcium