Scientific article

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

Published inEuropean journal of neuroscience, vol. 9, no. 12, p. 2605-2612
Publication date1997

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.

  • Animals
  • Brain Stem/cytology
  • Buffers
  • Calcium/ metabolism
  • Cyclic AMP/analogs & derivatives/metabolism/pharmacology
  • Enzyme Inhibitors/pharmacology
  • Excitatory Amino Acid Agonists/pharmacology
  • Forskolin/pharmacology
  • GTP-Binding Proteins/ metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
  • Hippocampus/cytology/metabolism
  • Male
  • N-Methylaspartate/pharmacology
  • Neurons/drug effects/metabolism/physiology
  • Oxytocin/ pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Thionucleotides/pharmacology
  • Vagus Nerve/cytology/drug effects/ physiology
Citation (ISO format)
ALBERI, Stefano, DREIFUSS, Jean-Jacques, RAGGENBASS, Mario. 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. In: European journal of neuroscience, 1997, vol. 9, n° 12, p. 2605–2612. doi: 10.1111/j.1460-9568.1997.tb01690.x
Main files (1)
ISSN of the journal0953-816X

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