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- Title
A direct inhibitory action of prostaglandins upon ACTH secretion at the late stages of the secretory pathway of AtT-20 cells.
- Authors
Wilson, Mary L.; Guild, Simon B.
- 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 (I nM-100 μM), guanosine-5'-O-(3-thiotriphosphate) (GTP-γ-S) (1 - 100 μM) and mastoparan ( I and 10 μM ) all stimulated ACTH secretion from permcabilized AtT-20 cells in a concentration-dependent manner. GTP-γ-S and mastoparan stimulated ACTH secretion from permeabilized cells in the absence of calcium. Co-incubation with prostaglandins E[subt] and E[sub2] (PGE[sub1], PGE[sub2]) (10 μM ) but not prostaglandin F[sub2x] (PGF[sub2x]) (10 μM ) significantly inhibited calcium-. GTP-γ-S and mastoparan-evoked secretion by 30-50%. 3 The effects of PGE[sub1] and PGE[sub2] upon GTP-γ-S (100 μM )-, calcium ( 10 μM )- and mastoparan (10 μM )-evoked secretion were concentration-dependent. PGE[sub1] significantly inhibited GTP-γ-S- and calcium-evoked secretion at concentrations of PGE[sub1] above 1 μM but mastoparan-evoked secretion only at the highest concentration of PGE[sub1] investigated (10 μ M). PGE[sub2] was much more potent than PGE[sub1] and significantly inhibited GTP-γ-S- and calcium-evoked secretion at 10 nM and above and mastoparan-evoked secretion above 1 μM. 4 The inhibitory effects of PGE[sub1] and PGE[sub2] upon calcium-, GTP-γ-S- and mastoparan-stimulated ACTH secretion from permeabilized cells were pertussis toxin (PTX) sensitive. 5 In intact cells PGE[sub1], PGE[sub2] and PGF[sub2x] (1 nM - 10 μM) acting singly had little or no effect upon ACTH secretion. However, only PGE[sub2] (1 nM -10 μM) 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.
- Subjects
ADRENOCORTICOTROPIC hormone; ANTERIOR pituitary gland; CALCIUM; PROSTAGLANDINS; G proteins; EXOCYTOSIS
- Publication
British Journal of Pharmacology, 2002, Vol 135, Issue 8, p1851
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0704652