Effect of prostaglandin E2 on ACTH and beta-endorphin release from rat adenohypophysis in vitro after secretagogues which can mimic various first or second messengers

Abstract

The purpose of the present study was to further characterize the inhibition by prostaglandin E2 (PGE2) of adrenocorticotropin (ACTH) and beta-endorphin release from rat anterior pituitary fragments in vitro. Peptide hormone release was induced by vasopressin, which initiates secretion via cell surface receptors, or by secretagogues which can mimic various post-receptor mechanisms and the effect of PGE2 was examined. Concentration-response curves of the effect of vasopressin on the release of beta-endorphin-like (beta-End-IR) and ACTH-like immunoreactivity (ACTH-IR) were constructed in the absence or presence of a fixed concentration of PGE2. The concentration-response curve of vasopressin was shifted to the right about 8-fold by PGE2 (1 mumol/l) without altering the maximum effect. PGE2 (60 nmol/l-1 mumol/l) markedly reduced beta-End-IR release induced by 8-bromoadenosine-3',5'-cyclic-monophosphate (8Br-cAMP) (1 mmol/l). Omission of Ca2+ from the incubation medium did not prevent PGE2-induced inhibition of 8Br-cAMP-evoked secretion. 4 beta-Phorbol, 12 beta-myristate, 13 alpha-acetate (PMA) stimulated beta-End-IR and ACTH-IR release in a concentration-dependent manner. This effect was not blocked by indometacin or eicosatetraynoic acid. PG E2 (greater than 100 nmol/l) reduced PMA (100 nmol/l)-elicited secretion by about 50%. PG E2 (1 mumol/l) almost halved beta-End-IR release caused by K+ (30 mmol/l). After pre-incubation in Ca2+-free medium, re-introduction of Ca2+ (1.3 mmol/l) elicited beta-End-IR release. This response was abolished by PG E2 (1 mumol/l). The addition of Ba2+ (10 mmol/l) to a Ca2+-free medium markedly enhanced beta-End-IR release.(ABSTRACT TRUNCATED AT 250 WORDS)