Induction of taurocholate release from isolated rat hepatocytes in suspension by alpha-adrenergic agents and vasopressin: implications for control of bile salt secretion.
Hepatocytes incubated with 25 muM [3H] taurocholate rapidly deplete the extracellular medium of [3H] taurocholate and achieve a steady-state level of intracellular bile salt within 15 min. Exposure of cells at steady state with extracellular taurocholate to the catecholamines norepinephrine or epinephrine results in release of 3H from the cells into the incubation medium; the 3H released represents almost exclusively unmetabolized [3H] taurocholate. The hierarchy of effectiveness of the catecholamines, norepinephrine congruent to epinephrine greater than phenylephrine much greater than isoproterenol, is indicative of an alpha-adrenergic mechanism. Induction of [3H] taurocholate release by norepinephrine is inhibited by the alpha-antagonists phenoxybenzamine and phentolamine and by chlorpromazine, but is not affected by the beta-antagonist propranolol, further supporting an alpha-adrenergic basis for this phenomenon. Arginine vasopressin, at concentrations of 1 X 10(-9) M and greater, also induces bile salt release. Classical alpha- and beta-antagonists have minimal effects on vasopressin induced bile salt release. While the peptide hormones angiotensin and oxytocin are, alone, relatively ineffective inducers of bile salt release, oxytocin potentiates the induction of bile salt release by vasopressin, suggesting complex interactions with membrane receptor function. Further studies assessing the interaction of sympathetic neurotransmitters and peptide hormones with bile salt transport and release in the hepatocyte may provide insight into the regulation of hepatic secretory function in the intact animal.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002395:Catecholamines / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001647:Bile Acids and Salts; D002395:Catecholamines; D006728:Hormones; D010455:Peptides; D014667:Vasopressins; D013656:Taurocholic Acid