Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Adenosine 3',5'-cyclic monophosphate-dependent release of prolactin from GH3 pituitary tumour cells. A quantitative analysis. 619 14

In Ca2+ -free EGTA-containing medium veratrine (3-25 microM) concentration-dependently enhanced the efflux of 3H-noradrenaline from (radiolabelled) rat neocortical slices. Clonidine (1 microM) inhibited and phentolamine (3 microM) enhanced veratrine-induced 3'-noradrenaline release and the modulatory effects were inversely related to the veratrine concentration used. Dibutyryl-cyclic AMP, 8-Bromo-cyclic AMP (10 microM--3 mM) and the adenylate cyclase activators NaF (2 mM) and forskolin (10 microM) enhanced 3H-noradrenaline release induced by 3 microM veratrine, but had no effect on spontaneous tritium efflux. In the presence of these drugs the modulatory effects of clonidine and phentolamine on 3H-noradrenaline release were reduced as expected from the enhanced efficacy of veratrine. In contrast to these drugs the selective cyclic AMP-phosphodiesterase inhibitor ZK 62771 reduced veratrine (3 microM)-induced 3H-noradrenaline release in Ca2+ -free medium. In the presence of 1.2 mM Ca2+, 3H-noradrenaline release induced by 13 mM K+ was also inhibited. However, when 3H-noradrenaline release was effected in the presence of tetrodotoxin (0.3 microM) or by electrical field-stimulation (1 Hz), ZK 62771 slightly but significantly enhanced the release. It is postulated that cyclic AMP is involved in the secretion process in central noradrenergic varicosities and that presynaptic alpha2-adrenoceptors upon activation inhibit the secretion process through an inhibition of a presynaptically located adenylate cyclase.
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PMID:3H-noradrenaline release from rat neocortical slices in the absence of extracellular Ca2+ and its presynaptic alpha 2-adrenergic modulation. A study on the possible role of cyclic AMP. 631 34

The present study extends our previous finding that the endothelium-independent relaxation in porcine coronary artery rings is enhanced after short-term (20 min) exposure to a physiological concentration (1 nM) of 17beta-estradiol and demonstrates that this effect may be attributable to activation of the cyclic AMP pathway. Isometric tension was recorded in isolated rings of porcine coronary arteries. Relaxation by levcromakalim and sodium nitroprusside, but not bradykinin and calcium ionophore A23187, were significantly potentiated following 20 min treatment with 1 nM 17beta-estradiol. This enhancing effect was insensitive to the transcriptional and translational inhibitors, actinomycin D and cycloheximide respectively and absent following repeated washing of the rings prior to construction of relaxation-response curves. The potentiating actions of 1 nM 17beta-estradiol on endothelium-independent relaxation were mimicked by the cyclic AMP analogue 8-Bromo-cyclic AMP and the protein kinase A activator Sp-cyclic AMPS but not by the cyclic GMP analogue 8-Bromo-cyclic GMP. The modulatory effect of 17beta-estradiol was increased in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The cyclic AMP-dependent protein kinase A inhibitor Rp-cyclic AMPS, but not the cyclic GMP antagonist Rp-8-Bromo-cyclic GMPS, effectively inhibited the enhancing effects 1 M 17beta-estradiol had on the relaxation responses of levcromakalim and sodium nitroprusside. These data support our earlier findings that physiologically relevant concentrations of 17beta-estradiol can acutely modify vasorelaxation in vitro. Furthermore, we report that this short-term effect of 17beta-estradiol on vasorelaxation appears to be mediated via non-genomic pathways and involves the cyclic AMP cascade.
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PMID:Enhanced relaxation of porcine coronary arteries after acute exposure to a physiological level of 17beta-estradiol involves non-genomic mechanisms and the cyclic AMP cascade. 1078 Sep 81