Galanin modulates vagally induced contractions in the mouse oesophagus.
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 micromol L(-1)) and SNAP37889 (100 nmol L(-1)), respectively, and the nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME) (200 micromol L(-1)), failed to affect this galanin-induced response. Simultaneous application of galantide (100 nmol L(-1)) and L-NAME (200 micromol L(-1)) significantly reduced the inhibitory effect of capsaicin (30 mumol 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.
Boudaka
A
A
Institute of Anatomy, University of Erlangen-Nuremberg, Erlangen, Germany.
Wörl
J
J
Shiina
T
T
Shimizu
Y
Y
Takewaki
T
T
Neuhuber
W L
WL
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology; D005260:Female; D019004:Galanin / Q000031:analogs & derivatives / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010618:Phenanthrolines / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D044088:Receptors, Galanin / Q000037:antagonists & inhibitors / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
C510288:1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-1H-indol-2-one; D000470:Alkaloids; D052117:Benzodioxoles; D004791:Enzyme Inhibitors; D007211:Indoles; D010618:Phenanthrolines; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D044088:Receptors, Galanin; D018689:Sensory System Agents; C074975:galantide; D013373:Substance P; D019004:Galanin; D002211:Capsaicin; C008922:piperine; D019331:NG-Nitroarginine Methyl Ester