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.

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 Adenosine 3′,5′-cyclic monophosphate-dependent release of prolactin from GH3 pituitary tumour cells. A quantitative analysis

1983 ◽  
Vol 216 (3) ◽  
pp. 551-557 ◽  
Author(s):  
S Guild ◽  
A H Drummond
Keyword(s):  
Quantitative Analysis ◽  
Cyclic Amp ◽  
Vasoactive Intestinal Polypeptide ◽  
Pituitary Tumour ◽  
Thyrotropin Releasing Hormone ◽  
Prolactin Release ◽  
Releasing Hormone ◽  
Gh3 Cell ◽  
Stimulation Of ◽  
Intestinal Polypeptide

The involvement of cyclic AMP in mediating regulatory peptide-controlled prolactin release from GH3 pituitary tumour cells was investigated. Cholera toxin and forskolin elicited concentration-dependent increases in both GH3 cell cyclic AMP content and prolactin release. The maximum rise in prolactin release with these agents was 2-fold over basal. 8-Bromo-cyclic AMP produced a similar stimulation of prolactin release. The phosphodiesterase inhibitor isobutylmethylxanthine also produced an increase in prolactin release and GH3 cell cyclic AMP content. However, the magnitude of the stimulated prolactin release exceeded that obtained with any other agent. Thyrotropin-releasing hormone (thyroliberin) and vasoactive intestinal polypeptide produced a concentration-dependent rise in both cell cyclic AMP content and prolactin release. However, only vasoactive intestinal polypeptide elicited an increase in cell cyclic AMP content at concentrations relevant to the stimulation of prolactin release. Vasoactive intestinal polypeptide and thyrotropin-releasing hormone, when used in combination, were additive with respect to prolactin release. Vasoactive intestinal polypeptide and forskolin, at concentrations that were maximal upon prolactin release, were, when used in combination, synergistic upon GH3 cell cyclic AMP content but were not additive upon prolactin release. In conclusion the evidence supports a role for cyclic AMP in the mediation of vasoactive intestinal polypeptide- but not thyrotropin-releasing hormone-stimulated prolactin release from GH3 cells. A quantitative analysis indicates that a 50-100% rise in cyclic AMP suffices to stimulate cyclic AMP-dependent prolactin release fully.

On the involvement of cyclic AMP and extracellular Ca2+ in the regulation of hormone release from rat pituitary tumour (GH3) cells in culture

1987 ◽  
Vol 7 (2) ◽  
pp. 93-105 ◽  
Author(s):  
Kjersti Sletholt ◽  
Egil Haug ◽  
Kaare M. Gautvik
Keyword(s):  
Cyclic Amp ◽  
Pituitary Tumour ◽  
Gh3 Cells ◽  
Ionophore A23187 ◽  
Channel Blockers ◽  
Hormone Release ◽  
Calmodulin Antagonist ◽  
Rat Pituitary ◽  
Combined Action ◽  
Dose Dependent

Thyroliberin (TRH), dibutyryl cyclic AMP (db-cAMP), and 3-isobutyl-l-methylxanthine (MIX) had a stimulatory effect on prolactin (PRL) and growth hormone (GH) release from GH 3 cells. Half-maximal and maximal effects were observed for TRH at 2.5 nM and 10 nM; for db-cAMP at 0.6 mM and 5 mM, respectively. MIX (0.1 mM-1 mM) induced a dose-dependent accumulation of cellular cyclic AMP, while the hormone release was already maximally stimulated at 0.1 mM MIX. The maximal effects on hormone release of TRH and db-cAMP, but not of TRH and MIX, were additive. The Ca2+ channel blockers Co2+ (5 mM) and verapamil (100 μM) and the Ca2+ chelator EGTA (4 mM) abolished the stimulatory effect of TRH (1 μM) on hormone release. Co2+ and verapamil, but not EGTA, inhibited the stimulatory effect of db-cAMP (5 mM) on hormone release. The inhibitory effects of Co2+ and verapamil on GH release were counteracted by the combination of TRH and db-cAMP. For PRL release Co2+, but not verapamil, was able to inhibit the combined action of TRH and db-cAMP. Co2+, verapamil, and EGTA eliminated the stimulatory effect of MIX (1 mM) on PRL release while only Co2+ and EGTA affected the GH release. Hormone release in the presence of MIX plus verapamil or EGTA, but not Co2+, was increased by TRH. The calmodulin antagonist trifluoperazine (TFP) at 30 μM inhibited basal hormone release and hormone release stimulated by TRH (1 μM), db-cAMP (5 mM), and MIX (1 mM). The Ca2+ ionophore A23187 (5 μM) had a stimulatory effect on basal hormone release which was abolished by 30 μM TFP.

Regulation of Thromboplastin Synthesis in Mouse Placental Cells In Vitro

1983 ◽  
Vol 50 (04) ◽  
pp. 831-834 ◽  
Author(s):  
Knut Dalaker ◽  
Hans Prydz
Keyword(s):  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Low Concentrations ◽  
Placental Cells ◽  
Dose Dependent ◽  
Higher Doses ◽  
Dose Dependent Effect ◽  
Methyl Xanthine

SummaryMouse placental cells are probably constitutive producers of the thromboplastin apoprotein in vitro. The effect of cyclic AMP- elevating compounds on their expression of thromboplastin activity has been studied. Dibutyryl cyclic AMP, the phosphodiesterase inhibitor Ro 20-1724 and the adenyl cyclase stimulator forskolin all decrease the synthesis of thromboplastin. Prostaglandin E2 and the phosphodiesterase inhibitor butyl-methyl-xanthine have a biphasic dose dependent effect. A stimulation was observed at low concentrations, whereas higher doses decreased the synthesis of thromboplastin. Adrenaline had no effect. Combination of two compounds, each at maximally inhibiting concentration gave no significant additive inhibitory effect, showing that they probably act via the same pathway.

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