Summary
The purpose of the present study was to further characterize the inhibition by prostaglandin E2 (PGE2) of adrenocorticotropin (ACTH) and β-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.
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1.
Concentration-response curves of the effect of vasopressin on the release of β-endorphin-like (β-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 μmol/l) without altering the maximum effect.
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2.
PGE2 (60 nmol/l–1 μmol/l) markedly reduced β-End-IR release induced by 8-bromoadenosine-3′,5′-cyclicmonophosphate (8Br-cAMP) (1 mmol/l). Omission of Ca2+ from the incubation medium did not prevent PGE2-induced inhibition of 8Br-cAMP-evoked secretion.
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3.
4β-Phorbol, 12β-myristate, 13α-acetate (PMA) stimulated β-End-IR and ACTH-IR release in a concentration-dependent manner. This effect was not blocked by indometacin or eicosatetraynoic acid. PG E2 (>100 nmol/l) reduced PMA (100 nmol/l)-elicited secretion by about 50%.
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4.
PG E2 (1 μmol/l) almost halved β-End-IR release caused by K+ (30 mmol/l).
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5.
After pre-incubation in Ca2+-free medium, re-introduction of Ca2+ (1.3 mmol/l) elicited β-End-IR release. This response was abolished by PG E2 (1 μmol/l).
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6.
The addition of Ba2+ (10 mmol/l) to a Ca2+-free medium markedly enhanced β-End-IR release. The stimulation by Ba2+ was blocked by elevating the Ca2+ concentration to 15.3 mmol/l. PGE2 (1 μmol/l) did not influence the Ba2+-induced secretion.
These data suggest that PGE2 inhibits receptor-mediated stimulation of β-End-IR/ACTH-IR release in an apparently competitive manner. We conclude that the ability of PGE2 to inhibit secretion from corticotrophs is not linked to a particular post-receptor mechanism but depends on the interference with a mechanism which follows second messenger formation and which, furthermore, is crucial for exocytotic release mechanisms, e.g. the intracellular availability of calcium.
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Knepel, W., Götz, D. Effect of prostaglandin E2 on ACTH and β-endorphin release from rat adenohypophysis in vitro after secretagogues which can mimic various first or second messengers. Naunyn-Schmiedeberg's Arch. Pharmacol. 333, 149–155 (1986). https://doi.org/10.1007/BF00506518
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DOI: https://doi.org/10.1007/BF00506518