INFLUENCE OF THYROID STATUS ON HEPATIC ALPHA(1)-ADRENORECEPTOR RESPONSIVENESS

The present work aimed to elucidate the influence of thyroid functiona l status on the alpha(1)-adrenoreceptor-induced activation of hepatic metabolic functions. The experiments were performed in either a nonrec irculating liver perfusion system featuring continuous monitoring of p ortal pressure, PO2, pCa, and pH, or isolated hepatocytes from euthyro id, hyperthyroid, and hypothyroid rats. Hypothyroidism decreased the a lpha (1)-adrenergic stimulation of respiration, glycogen breakdown, an d gluconeogenesis. These effects were accompanied by a decreased intra cellular Ca2+ mobilization corroborating that those processes are regu lated by the Ca2+-dependent branch of the alpha(1)-adrenoreceptor sign aling pathway. Moreover, in hyperthyroid rats the alpha(1)-adrenergic- induced increase in cytosolic Ca2+ was enhanced, and glucose synthesis or mobilization was not altered. The thyroid status influenced neithe r the alpha(1)-adrenergic stimulation of vascular smooth muscle contra ction nor the alpha(1)-agonist-induced intracellular alkalinization an d protein kinase C (PKC) activation. Thus the distinct impairment of t he Ca2+-dependent branch of the alpha(1)-adrenoreceptor signaling path way by thyroid status provides a useful tool to investigate the role p layed by each signaling pathway, Ca2+ or PKC, in controlling hepatic f unctions.