Inhibition of p-nitrophenol glucuronidation by calcium mobilizing hormones.
1. Vasopressin and phenylephrine markedly inhibited the glucuronidation of p-nitrophenol in isolated murine hepatocytes. 2. After longer preincubation of hepatocytes in the presence of vasopressin or phenylephrine the rate of conjugation began to return to the control values indicating the reversibility of the inhibition caused by these agents. 3. The inhibitory effect of both agents was dependent on the Ca2+ filled state of the intracellular stores. 4. The inhibition caused by the alpha 1 receptor agonist phenylephrine was receptor mediated because it could be prevented by the addition of alpha 1 antagonist prazosin. 5. The data support the theory that the maintenance of the intralumenal Ca2+ concentration is necessary for the optimal activity of p-nitrophenol UDP-glucuronosyl-transferase.
Braun
L
L
1st Institute of Biochemistry, Semmelweis Medical University, Budapest, Hungary.
Fulceri
R
R
Benedetti
A
A
Mandl
J
J
Bánhegyi
G
G
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003864:Depression, Chemical; D005965:Glucuronates / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism*; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D005965:Glucuronates; D006728:Hormones; D009596:Nitrophenols; D014667:Vasopressins; D010656:Phenylephrine; D002118:Calcium; D011224:Prazosin; C024836:4-nitrophenol