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Keywords:

  • capsaicin;
  • co-innervation;
  • enteric neurons;
  • galanin;
  • galantide;
  • motor endplate

Abstract  Nitrergic myenteric neurons co-innervating motor endplates were previously shown to inhibit vagally induced contractions of striated muscle in the rodent oesophagus. Immunohistochemical demonstration of putative co-transmitters, e.g. galanin, in enteric neurons prompted us to study a possible role of galanin in modulating vagally mediated contractions in an in vitro vagus nerve-oesophagus preparation of the mouse. Galanin (1–16) (1–100 nmol L−1), in the presence of the peptidase inhibitor, phenanthroline monohydrate, inhibited vagally induced contractions in a concentration-dependent manner (control: 100%; galanin 1 nmol L−1: 95.6 ± 1.6%; galanin 10 nmol L−1: 57.3 ± 6.5%; galanin 100 nmol L−1: 31.2 ± 8.1%, n = 5). The non-selective galanin receptor antagonist, galantide (100 nmol L−1), blocked the inhibitory effect of galanin (10 nmol L−1) while the selective non-galanin receptor 1 and galanin receptor 3 antagonists, M871 (1 μmol L−1) and SNAP37889 (100 nmol L−1), respectively, and the nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME) (200 μmol L−1), failed to affect this galanin-induced response. Simultaneous application of galantide (100 nmol L−1) and l-NAME (200 μmol L−1) significantly reduced the inhibitory effect of capsaicin (30 μmol L−1) on vagally induced contractions when compared with its effect in the presence of l-NAME alone or in combination with the selective galanin receptor 2 or 3 antagonists. An inhibitory effect of piperine on vagally induced contractions was reduced neither by galantide nor by l-NAME. Immunohistochemistry revealed galanin immunoreactive myenteric neurons and nerve fibres intermingling with cholinergic vagal terminals at motor endplates. These data suggest that galanin from co-innervating enteric neurons co-operates with nitric oxide in modulating vagally induced contractions in the mouse oesophagus.