Open AccessPertussis toxin abolishes the inhibitory effects of prostaglandins E 1 , E 2 ,I 2 and F 2α on hormone‐induced cAMP accumulation in cultured hepatocytes
Author(s) -
MELIEN Øyvind,
WINSNES Randi,
REFSNES Magne,
GLADHAUG Ivar P.,
CHRISTOFFERSEN Thoralf
Publication year - 1988
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1988.tb13886.x
Subject(s) - pertussis toxin , glucagon , medicine , endocrinology , cholera toxin , chemistry , histamine , cyclase , alpha (finance) , g protein , prostaglandin e2 , stimulation , prostaglandin e , prostaglandin , epinephrine , hormone , biology , receptor , construct validity , nursing , patient satisfaction
Several prostaglandins inhibit the cAMP response to glucagon and β‐adrenergic stimulation in hepatocytes. To probe the mechanism of this inhibition, we have examined in primary hepatocyte cultures how pretreatment with pertussis toxin (islet‐activating protein) influences the ability of the cells to respond to hormones and prostaglandins. Pertussis toxin augmented the effects of glucagon, epinephrine and isoproterenol, and also markedly enhanced the cAMP response to prostaglandin E 1 (PGE 1 ). Furthermore, whereas PGE 1 , PGE 2 , PGI 2 and PGF 2α , attenuated the cAMP responses to glucagon in control cultures, this inhibition was abolished in cells pretreated with pertussis toxin. A more detailed comparison was made of the effects of PGE 1 and PGF 2α . In cells not treated with pertussis toxin, both these prostaglandins at high concentrations reduced the cAMP response to glucagon and isoproterenol by approximately 50%, but dose‐effect curves showed that PGE 1 was about 100‐fold more potent as an inhibitor than PGF 2α . Pertussis toxin abolished the inhibitory effects of PGE 1 and PGF 2α with almost identical time and dose requirements. The results obtained with PGE 1 , PGE 2 , PG 1 , and PGF 2α suggest that prostaglandins of different series attenuate hormone‐activable adenylate cyclase in hepatocytes through a common mechanism, dependent on the inhibitory GTP‐binding protein.