pituitrin and 4-nitrophenol

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.

Topics: Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Calcium; Depression, Chemical; Glucuronates; Hormones; In Vitro Techniques; Liver; Male; Mice; Mice, Inbred Strains; Microsomes, Liver; Nitrophenols; Phenylephrine; Prazosin; Vasopressins

On incubation with a tyrosinase preparation at pH 7.5, oxytocin and vasopressin were inactivated. The loss of oxytocic activity did not differ significantly from that of milk-ejecting activity in oxytocin, nor the loss of pressor activity from that of antidiuretic activity in vasopressin. Oxytocin was inactivated less rapidly at pH 6.6 than at pH 7.5. At pH 3.9 neither oxytocin nor vasopressin was inactivated. Analogues of oxytocin and vasopressin, in which tyrosine is replaced by phenylalanine, were not inactivated by the tyrosinase preparation used. On incubation of bradykinin with two different tyrosinase preparations, there was no loss of oxytocic activity at pH 7.5 but an almost total loss at pH 3.9. In the presence of p-nitrophenol, ascorbic acid, sodium diethyldithiocarbamate and during incubation under anaerobic conditions the inactivation of oxytocin at pH 7.5 was inhibited, but not that of bradykinin at pH 3.9. It is concluded that the tyrosinase preparations used contain two distinct enzymes or activities, the one inactivating oxytocin and vasopressin at pH 7.5 and the other bradykinin at pH 3.9.

Topics: Arginine Vasopressin; Ascorbic Acid; Bradykinin; Catechol Oxidase; Kallikreins; Monophenol Monooxygenase; Nitrophenols; Oxidoreductases; Oxytocics; Oxytocin; Phenylalanine; Tyrosine; Vasoconstrictor Agents; Vasopressins