Oxytocin-induced sodium current is mediated by cAMP-dependent protein phosphorylation in an identified snail neuron.
The intracellular biochemical process underlying oxytocin-induced change of membrane properties was analyzed in an identified neuron of Achatina fulica Férussac, using pressure injection technique and pharmacological tools. Oxytocin dose-dependently enhanced the negative slope resistance (NSR) region on the current-voltage relation. The oxytocin-induced current was attenuated by a reduction of extracellular Na+ and not influenced by the addition of 100 microM tetrodotoxin (TTX) to the medium, suggesting that this current is predominantly due to the activation of TTX-resistant Na+ channels. In the Ca2(+)-free state, substituted by an equivalent amount of Co2+, the amplitude of oxytocin-induced current was somewhat reduced at the NSR region but it was not influenced at less than -60 mV. Application of 100 microM isobutylmethylxanthine, a phosphodiesterase inhibitor, augmented the oxytocin-induced current. Pressure injection of 10 mM adenosine 3',5'-cyclic monophosphate (cAMP) elicited a Na(+)-dependent inward current similar to the oxytocin response. The further role of cAMP linked with the oxytocin-induced current was investigated using two kinds of cAMP-dependent protein kinase inhibitors, isoquinolinesulfonamide (H-8) and protein kinase inhibitor (PKI). Extracellular application of H-8 or pressure injection of PKI, prior to oxytocin application, both blocked the oxytocin-induced current. Based on these results, oxytocin-elicited inward currents may mediate cAMP-dependent protein phosphorylation mainly by activation of Na+ channels.
Department of Physiology, Gifu University School of Medicine, Japan.
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology*; D010766:Phosphorylation; D012908:Snails / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000502:physiology*
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C015482:protein kinase modulator; D010121:Oxytocin; D012964:Sodium; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine