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Title

The oxytocin-induced inward current in vagal neurons of the rat is mediated by G protein activation but not by an increase in the intracellular calcium concentration

Authors
Dreifuss, Jean-Jacques
Published in European Journal of Neuroscience. 1997, vol. 9, no. 12, p. 2605-2612
Abstract The neuropeptide oxytocin can depolarize parasympathetic preganglionic neurons in the dorsal motor nucleus of the vagus nerve of the rat by generating a sustained inward current, which is sodium-dependent and tetrodotoxin-insensitive. The second messenger activated by oxytocin receptor binding is, however, not yet known. In the present study, we attempted to characterize it by using the whole-cell recording technique and brainstem slices. When loaded with GTP-gamma-S, a non-hydrolysable analogue of GTP, vagal neurons generated a persistent inward current in the absence of agonist and the oxytocin effect was suppressed, suggesting that the peptide-evoked current was mediated by G-protein activation. Loading vagal neurons with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid (BAPTA) suppressed a calcium-dependent, slowly decaying potassium aftercurrent but did not affect the oxytocin response, suggesting that the latter was not mediated by an agonist-induced increase in the intracellular calcium concentration. Protein kinase C (PKC) activation was probably not involved, since the peptide-evoked current was not modified by loading neurons with the PKC inhibitor H7. Thus, the oxytocin-evoked current in vagal neurons was probably not mediated by phospholipase C-beta (PLC-beta) activation. Loading neurons with 8-Br-cAMP or with an adenylyl cyclase activator (forskolin) reduced the oxytocin-evoked current by about half. SQ 22536, an adenylyl cyclase inhibitor, reduced this current by a similar amount. However, the peptide-evoked current was unaffected by Rp-cAMPS and Sp-cAMPS, an inhibitor and an activator, respectively, of cAMP-dependent protein kinase (PKA). We suggest that oxytocin activates two distinct signalling pathways in vagal neurons: one which is cAMP-dependent, but PKA-independent, and one, unidentified, which is PLC-beta-and cAMP-independent. Each pathway accounts for about half of the peptide effect and both appear to involve G-protein activation.
Keywords AnimalsBrain Stem/cytologyBuffersCalcium/ metabolismCyclic AMP/analogs & derivatives/metabolism/pharmacologyEnzyme Inhibitors/pharmacologyExcitatory Amino Acid Agonists/pharmacologyForskolin/pharmacologyGTP-Binding Proteins/ metabolismGuanosine 5'-O-(3-Thiotriphosphate)/pharmacologyHippocampus/cytology/metabolismMaleN-Methylaspartate/pharmacologyNeurons/drug effects/metabolism/physiologyOxytocin/ pharmacologyPatch-Clamp TechniquesRatsRats, Sprague-DawleyThionucleotides/pharmacologyVagus Nerve/cytology/drug effects/ physiology
Stable URL http://archive-ouverte.unige.ch/unige:10157
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PMID: 9517466
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