Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of the phosphodiesterase inhibitors theophylline and isobutylmethylxanthine (IBMX) on baseline and voltage-activated Cl- conductance (gCl) of toad skin were compared with those of the potent 2-chlorophenylthio analogue of cAMP (CPT-cAMP). 2. Using intact and split skins of Bufo viridis we confirmed that theophylline and IBMX raised the voltage-activated gCl with a pattern identical to that seen under control conditions. This effect was small or missing if gCl was already high in the control. 3. CPT-cAMP, in contrast, increased the Cl(-)-specific conductance by up to 6 mS cm-2 at short circuit. The characteristic time-dependent, slow activation of gCl by serosa-positive clamp potentials was completely lost under these conditions. 4. Coinciding with the loss of voltage activation of gCl the plateau value of the Lorentzian component of fluctuation in current at serosa-positive clamp potentials decreased by almost 50%. The corner frequencies were not notably different. 5. After CPT-cAMP, the sigmoidal voltage-conductance relation that is characteristic of control conditions or after theophylline disappeared; the patterns were variable and incompatible with voltage activation. 6. The voltage-activated gCl under control conditions and with theophylline was blocked by mucosal NO3-, I- or SCN-, the last two being almost equally effective. In the presence of CPT-cAMP, mucosal NO3- had minimal influence on tissue conductance, whereas the effects of I- and SCN- were essentially unchanged. Br- on the mucosal side could substitute for Cl- under all conditions. 7. The results suggest that protein phosphorylation by supramaximal concentrations of cAMP induces maximal conductance through anion-specific routes, while the voltage sensitivity of this pathway is lost. The effects of theophylline and IBMX on the voltage-activated Cl-conductance of toad skin cannot be explained solely by inhibition of the phosphodiesterase.
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PMID:Effects of cyclic AMP and theophylline on chloride conductance across toad skin. 858 95

1. The objective of this study was to investigate the mechanism of PGE2 regulation of Cl- transport across glandular endometrial cells grown in primary culture. 2. Most of the basal short circuit current (Isc) was inhibited by luminal addition of 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) or glibenclamide, suggesting the presence of a basally active Cl- conductance in the apical membrane. 3. Basolateral addition of 10 microM PGE2 increased Isc by 41 +/- 3 microA. A similar response was observed when cells were treated with 8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate (CPT-cAMP). Pretreatment of monolayers with NPPB and glibenclamide blocked the PGE2 and cAMP-mediated increase in Isc, suggesting that the effects of PGE2 and cAMP were dependent on the activity of an apical NPPB- and glibenclamide-sensitive conductance. 4. Addition of 50 nM antiPGE2 antibody to the basolateral bathing solution decreased basal Isc by 20 % and shifted the threshold response to exogenous PGE2. This result suggests autocrine regulation of electrogenic Cl- transport by PGE2. 5. Experiments with amphotericin B-permeabilized monolayers revealed that the apical PGE2-activated, NPPB- and glibenclamide-sensitive conductance was Cl- dependent and that the current-voltage relationship and anion permeation properties (SCN->Br- > Cl- > I-) were characteristic of the cystic fibrosis transmembrane conductance regulator (CFTR). 6. Cultured porcine endometrial epithelial cells were specifically labelled with an antibody to a peptide sequence within the regulatory domain of CFTR. 7. The effect of PGE2 was blocked by basolateral addition of bumetanide and furosemide at concentrations that are selective for inhibition of Na+-K+-2Cl-cotransport activity. The effect of bumetanide on Isc was Cl- dependent, suggesting a role for the bumetanide-sensitive transport pathway in Cl- secretion. 8. PGE2 and cAMP also activated an outwardly rectifying basolateral K+ channel which presumably sustains the driving force for electrogenic Cl- efflux across the apical membrane. 9. The concentration-conductance and concentration-Isc response relationships for PGE2 showed that basolateral K+ permeability was rate limiting with respect to transepithelial anion secretion and that activation of a basolateral K+ channel by PGE2 was necessary to achieve maximum rates of Cl- secretion.
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PMID:Regulation of chloride secretion across porcine endometrial epithelial cells by prostaglandin E2. 949 Aug 13