Phorbol ester-induced inhibition of vasoactive intestinal polypeptide-stimulated cyclic AMP accumulation in GH3 pituitary tumour cells

1985 ◽  
Vol 13 (4) ◽  
pp. 786-787
Author(s):  
L. A. QUILLIAM ◽  
P. R. M. DOBSON ◽  
B. L. BROWN
Keyword(s):  
Cyclic Amp ◽  
Phorbol Ester ◽  
Vasoactive Intestinal Polypeptide ◽  
Pituitary Tumour ◽  
Tumour Cells ◽  
Cyclic Amp Accumulation ◽  
Intestinal Polypeptide

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 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.

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