scholarly journals Pertussis toxin blocks the inhibitory effect of muscarinic cholinergic agonists on cyclic AMP accumulation and prolactin secretion in GH3 anterior-pituitary tumour cells

1984 ◽  
Vol 223 (1) ◽  
pp. 145-149 ◽  
Author(s):  
B L Brown ◽  
R J H Wojcikiewicz ◽  
P R M Dobson ◽  
A Robinson ◽  
L I Irons
Keyword(s):  
Cyclic Amp ◽  
Pertussis Toxin ◽  
Anterior Pituitary ◽  
Pituitary Tumour ◽  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Gh3 Cells ◽  
Muscarinic Agonists ◽  
Cyclic Amp Accumulation ◽  
Muscarinic Cholinergic

The inhibition of prolactin secretion and cyclic AMP accumulation in GH3 cells by muscarinic agonists was blocked by preincubation of the cells with pertussis toxin (islet-activating protein). There was a lag of approx. 80 min in the onset of the effect on secretion. These results suggest that muscarinic agonists decrease prolactin secretion by inhibiting adenylate cyclase activity.

scholarly journals Vasoactive-intestinal-polypeptide-stimulated adenosine 3′,5′-cyclic monophosphate accumulation in GH3 pituitary tumour cells. Reversal of desensitization by forskolin

1984 ◽  
Vol 221 (3) ◽  
pp. 789-796 ◽  
Author(s):  
S Guild ◽  
A H Drummond
Keyword(s):  
Cyclic Amp ◽  
Vasoactive Intestinal Polypeptide ◽  
Regulatory Protein ◽  
Phosphodiesterase Inhibitor ◽  
Pituitary Tumour ◽  
Tumour Cells ◽  
Gh3 Cells ◽  
Low Concentrations ◽  
Cyclic Amp Accumulation ◽  
Intestinal Polypeptide

The interaction between forskolin and vasoactive intestinal polypeptide (VIP) in the regulation of cyclic AMP production in GH3 pituitary tumour cells was investigated. Both forskolin (10nM-10 microns) and VIP (10pM-10nM) increased the cyclic AMP content of GH3 cells. Forskolin (50-100nM) was additive with VIP in stimulating cyclic AMP accumulation when low concentrations (less than 1 nM) of the peptide were used, but exhibited a synergistic interaction with higher VIP concentrations (10-100 nM). These effects on cyclic AMP accumulation were reflected in a leftward shift in the concentration-response curve for VIP-stimulated prolactin release from GH3 cells, a process known to be regulated by intracellular cyclic AMP concentrations. The synergy observed did not appear to be related to changes in cyclic nucleotide phosphodiesterase activity, since it was even more marked in the presence of isobutylmethylxanthine, a phosphodiesterase inhibitor. Studies of the time-course of VIP-induced changes in GH3-cell cyclic AMP content revealed that, with high concentrations of VIP, production ceased within 2 min of addition. This attenuation of cyclic AMP synthesis was still observed in the presence of isobutylmethylxanthine, but was markedly inhibited by low concentrations of forskolin (50-100nM). The results suggest that VIP-induced cyclic AMP production rapidly becomes desensitized. This process, which is prevented by forskolin, may be related to changes in the ability of the guanine nucleotide regulatory protein to couple receptor occupancy to activation of adenylate cyclase.

The effect of nifedipine on CRF-41 and AVP-induced ACTH release in vitro

1985 ◽  
Vol 109 (1) ◽  
pp. 32-36 ◽  
Author(s):  
Kazuharu Murakami ◽  
Kozo Hashimoto ◽  
Zensuke Ota
Keyword(s):  
Cyclic Amp ◽  
Calcium Ions ◽  
Anterior Pituitary ◽  
Inhibitory Effect ◽  
Extracellular Calcium ◽  
Pituitary Cells ◽  
Amp System ◽  
Cyclic Amp Accumulation ◽  
Acth Release

Abstract. The effect of nifedipine on CRF-41- and AVP-induced ACTH release was examined using monolayer cultured rat anterior pituitary cells and pituitary halves. Nifedipine inhibited ACTH release induced by synthetic rat CRF-41 in two systems. In pituitary halves, CRF-41 significantly stimulated both ACTH release and cyclic AMP accumulation. Nifedipine inhibited CRF-41-induced ACTH release and the inhibitory effect of nifedipine on CRF-41-induced ACTH release was accompanied by parallel decrease of cyclic AMP levels in pituitary halves. Nifedipine did not inhibit AVP-induced ACTH release in pituitary halves, and AVP did not significantly affect cyclic AMP accumulation in pituitary halves. These results suggest that CRF-41 stimulates ACTH release through the intracellular cyclic AMP system and calcium-calmodulin system which are accelerated by the influx of extracellular calcium ions. Moreover, it is suggested that the calcium required for AVP-induced ACTH release is derived primarily from intracellular rather than extracellular sources.

Pertussis toxin uncouples dopamine agonist inhibition of prolactin release

1983 ◽  
Vol 244 (5) ◽  
pp. E499-E504 ◽  
Author(s):  
M. J. Cronin ◽  
G. A. Myers ◽  
R. M. MacLeod ◽  
E. L. Hewlett
Keyword(s):  
Cyclic Amp ◽  
Dopamine Agonist ◽  
Pertussis Toxin ◽  
Anterior Pituitary ◽  
Prolactin Secretion ◽  
Pituitary Cells ◽  
Prolactin Release ◽  
Pituitary Prolactin ◽  
Hormone System

Pertussis toxin, a protein exotoxin produced by Bordetella pertussis, markedly reduced or eliminated the ability of dopamine or the dopamine agonist bromocriptine to inhibit prolactin release from anterior pituitary cells in vitro. Toxin-mediated reversal of the effect on dopamine agonist inhibition of prolactin release occurred with a lag of greater than 6 h, was maximal by 24 h, and persisted for at least 6 days after removal of the toxin from the medium. The toxin reduced dopamine agonist efficacy without altering potency or directly modifying the dopamine receptor (as measured by [3H]spiperone binding). The ability of dopamine to reduce cellular cyclic AMP content was also antagonized by pertussis toxin, supporting the hypothesis that reduction of cellular cyclic AMP content and inhibition of prolactin secretion may be causally related. These data demonstrated that pertussis toxin can prevent the typical inhibitory action of dopamine agonists on anterior pituitary prolactin release and suggest that this receptor-mediated inhibitory hormone system is analogous to other inhibitory receptors coupled to adenylate cyclase.

scholarly journals Effects of dopamine on prolactin secretion and cyclic AMP accumulation in the rat anterior pituitary gland

1981 ◽  
Vol 194 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Keith P. Ray ◽  
Michael Wallis
Keyword(s):  
Cyclic Amp ◽  
Cholera Toxin ◽  
Anterior Pituitary ◽  
Phosphodiesterase Inhibitors ◽  
Prolactin Secretion ◽  
Significant Inhibition ◽  
Female Rats ◽  
Control Value ◽  
Cyclic Amp Accumulation

The effects of dopamine on pituitary prolactin secretion and pituitary cyclic AMP accumulation were studied by using anterior pituitary glands from adult female rats, incubated in vitro. During 2h incubations, significant inhibition of prolactin secretion was achieved at concentrations between 1 and 10nm-dopamine. However, 0.1–1μm-dopamine was required before a significant decrease in pituitary cyclic AMP content was observed. In the presence of 1μm-dopamine, pituitary cyclic AMP content decreased rapidly to reach about 75% of the control value within 20min and there was no further decrease for at least 2h. Incubation with the phosphodiesterase inhibitors theophylline (8mm) or isobutylmethylxanthine (2mm) increased pituitary cyclic AMP concentrations 3- and 6-fold respectively. Dopamine (1μm) had no effect on the cyclic AMP accumulation measured in the presence of theophylline, but inhibited the isobutylmethylxanthine-induced increase by 50%. The dopamine inhibition of prolactin secretion was not affected by either inhibitor. Two derivatives of cyclic AMP (dibutyryl cyclic AMP and 8-bromo cyclic AMP) were unable to block the dopamine (1μm) inhibition of prolactin secretion, although 8-bromo cyclic AMP (2mm) significantly stimulated prolactin secretion and both compounds increased somatotropin (growth hormone) release. Cholera toxin (3μg/ml for 4h) increased pituitary cyclic AMP concentrations 4–5-fold, but had no effect on prolactin secretion. The inhibition of prolactin secretion by dopamine was unaffected by cholera toxin, despite the fact that dopamine had no effect on the raised pituitary cyclic AMP concentration caused by this factor. Dopamine had no significant effect on either basal or stimulated somatotropin secretion under any of the conditions tested. We conclude that the inhibitory effects of dopamine on prolactin secretion are probably not mediated by lowering of cyclic AMP concentration, although modulation of the concentration of this nucleotide in some other circumstances may alter the secretion of the hormone.

Prolactin secretion and dopamine receptors of the MtTW15 transplantable pituitary tumour

1982 ◽  
Vol 94 (3) ◽  
pp. 347-NP ◽  
Author(s):  
M. J. Cronin ◽  
D. A. Keefer ◽  
C. A. Valdenegro ◽  
L. G. Dabney ◽  
R. M. MacLeod
Keyword(s):  
Pituitary Gland ◽  
Dopamine Receptors ◽  
Anterior Pituitary ◽  
Pituitary Tumour ◽  
Prolactin Secretion ◽  
Tumour Cells ◽  
Dopamine Antagonist ◽  
Cell Column ◽  
Prolactin Release

The MtTW15 transplantable pituitary tumour grown in rats was tested in vitro for the ability of dopamine agonists to affect prolactin secretion and for the existence of dopamine receptors. Prolactin release from enzymatically dispersed cells and non-enzymatically treated tissue fragments of both the tumour and the anterior pituitary gland was determined in a cell perifusion column apparatus. Dopamine (0·1–5 μmol/l), bromocriptine (50 nmol/l) and the dopamine antagonist haloperidol (100 nmol/l) had no effect on prolactin release from the tumour cells. In contrast, dopamine (500 nmol/l) inhibited prolactin secretion from normal anterior pituitary cells in a parallel cell column and haloperidol blocked this inhibition. Although oestrogen treatment in vivo stimulated prolactin release in vitro when the tumour was removed and studied in the cell column, oestrogen had no effect on the inability of dopamine to modify the prolactin secretion. Growth hormone release from the tumour cells was not affected by dopamine. Although MtTW15 cells were refractory to dopaminergic inhibition of prolactin release, the dopamine receptors present in tumour homogenates were indistinguishable from the dopamine receptors previously defined in the normal anterior pituitary gland. The binding of the dopamine antagonist [3H]spiperone to the tumour was saturable (110 fmol/mg protein), of high affinity to one apparent class of sites (dissociation constant = 0·12 nmol/l), reversible and sensitive to guanine nucleotides. The pharmacology of the binding was defined in competition studies with a large number of agonists and antagonists. From the order of potency of these agents, a dopaminergic interaction was apparent. We conclude that the prolactin-secreting MtTW15 tumour cells appear to be completely unresponsive to dopamine or to the potent dopamine agonist bromocriptine, in spite of apparently normal dopamine receptors in the tumour.

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