title: A direct inhibitory action of prostaglandins upon ACTH secretion at the late stages of the secretory pathway of AtT-20 cells.
abstract: 1. The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used as a model system for the study of the effects of prostaglandins upon the late stages of the adrenocorticotrophin (ACTH) secretory pathway. 2. Calcium (1 nM - 100 microM), guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) (1 - 100 microM) and mastoparan (1 and 10 microM) all stimulated ACTH secretion from permeabilized AtT-20 cells in a concentration-dependent manner. GTP-gamma-S and mastoparan stimulated ACTH secretion from permeabilized cells in the absence of calcium. Co-incubation with prostaglandins E(1) and E(2) (PGE(1), PGE(2)) (10 microM) but not prostaglandin F(2 alpha) (PGF(2 alpha)) (10 microM) significantly inhibited calcium-, GTP-gamma-S and mastoparan-evoked secretion by 30 - 50%. 3. The effects of PGE(1) and PGE(2) upon GTP-gamma-S (100 microM)-, calcium (10 microM)- and mastoparan (10 microM)-evoked secretion were concentration-dependent. PGE(1) significantly inhibited GTP-gamma-S- and calcium-evoked secretion at concentrations of PGE(1) above 1 microM but mastoparan-evoked secretion only at the highest concentration of PGE(1) investigated (10 microM). PGE(2) was much more potent than PGE(1) and significantly inhibited GTP-gamma-S- and calcium-evoked secretion at 10 nM and above and mastoparan-evoked secretion above 1 microM. 4. The inhibitory effects of PGE(1) and PGE(2) upon calcium-, GTP-gamma-S- and mastoparan-stimulated ACTH secretion from permeabilized cells were pertussis toxin (PTX) sensitive. 5. In intact cells PGE(1), PGE(2) and PGF(2 alpha) (1 nM - 10 microM) acting singly had little or no effect upon ACTH secretion. However, only PGE(2) (1 nM - 10 microM) significantly inhibited corticotrophin-releasing factor-41 (CRF-41) (100 nM)-evoked secretion in a concentration dependent manner. 6. The present study finds that prostaglandins of the E series exert an inhibitory action, via a pertussis toxin-sensitive GTP-binding (G)-protein, in the late stages of the ACTH secretory pathway distal to the G-exocytosis (Ge)/calcium point of control.
authors.affiliation: Molecular Endocrinology Group, School of Biology, Bute Medical Building, University of St. Andrews, St Andrews KY16 9TS, UK.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Wilson
authors.forename: Simon B
authors.initials: SB
authors.lastname: Guild
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000527:Alprostadil / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002458:Cell Fractionation; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D010455:Peptides; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; D000324:Adrenocorticotropic Hormone; D015237:Dinoprost; D037342:Pertussis Toxin; D000527:Alprostadil; D015232:Dinoprostone; D002118:Calcium