3':5'-cyclic guanosine monophosphate (cGMP) potentiates the inositol 1,4,5-trisphosphate-evoked Ca2+ release in guinea-pig hepatocytes.
The effect of cGMP on noradrenaline-induced intracellular Ca2+ mobilization was investigated in whole-cell voltage-clamped guinea-pig hepatocytes. Treatment of the cells with 8-Br-cGMP (1-500 microM) resulted in an increase in the sensitivity of the cells to noradrenaline and to inositol 1,4,5-trisphosphate (InsP3) photo-released from caged InsP3. The positive effect of 8-Br-cGMP on the Ca2+ release evoked by Ca(2+)-mobilizing agonists or InsP3 was blocked by a protein kinase G (PKG; cGMP-dependent protein kinase) inhibitor, the RP-8-(4-chlorophenylthio)guanosine 3':5'-monophosphorothioate. 8-Br-cGMP affected neither the basal InsP3 concentration nor the noradrenaline-induced production of InsP3. In permeabilized hepatocytes, the dose-response curve for InsP3-induced Ca2+ release was shifted to the left in the presence of 8-Br-cGMP. Furthermore, the treatment with 8-Br-cGMP did not affect the Ca2+ content of the InsP3-sensitive Ca2+ stores. These results indicate that intracellular cGMP potentiates the noradrenaline-induced Ca2+ response by enhancing Ca2+ release from the intracellular Ca2+ stores. We suggest that cGMP increases the apparent affinity of InsP3 receptors for InsP3 in guinea-pig hepatocytes probably by phosphorylation via the activation of PKG.
Guihard
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INSERM U442, Bâtiment 443, UPS, Orsay, France.
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Capiod
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D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004357:Drug Synergism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010782:Photolysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C016276:8-bromocyclic GMP; D015544:Inositol 1,4,5-Trisphosphate; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium; D009638:Norepinephrine