Evidence for a modulatory role of orexin A on the nitrergic neurotransmission in the mouse gastric fundus.
The presence of orexins and their receptors in the gastrointestinal tract supports a local action of these peptides. Aim of the present study was to investigate the effects of orexin A (OXA) on the relaxant responses of the mouse gastric fundus. Mechanical responses of gastric strips were recorded via force-displacement transducers. The presence of orexin receptors (OX-1R) was also evaluated by immunocytochemistry. In carbachol precontracted strips and in the presence of guanethidine, electrical field stimulation (EFS) elicited a fast inhibitory response that may be followed, at the highest stimulation frequencies employed, by a sustained relaxation. All relaxant responses were abolished by TTX. The fast response was abolished by the nitric oxide (NO) synthesis inhibitor l-NNA (2x10(-4) M) as well as by the guanylate cyclase inhibitor ODQ (1x10(-6) M). OXA (3x10(-7) M) greatly increased the amplitude of the EFS-induced fast relaxation without affecting the sustained one. OXA also potentiated the amplitude of the relaxant responses elicited by the ganglionic stimulating agent DMPP (1x10(-5) M), but had no effects on the direct smooth muscle relaxant responses elicited by papaverine (1x10(-5) M) or VIP (1x10(-7) M). In the presence of l-NNA, the response to DMPP was reduced in amplitude and no longer influenced by OXA. The OX1 receptor antagonist SB-334867 (1x10(-5) M) reduced the amplitude of the EFS-induced fast relaxation without influencing neither the sustained responses nor those to papaverine and VIP. Immunocytochemistry showed the presence of neurons that co-express neuronal nitric oxide synthase and OX-1R. These results indicate that, in mouse gastric fundus, OXA exerts a modulatory action at the postganglionic level on the nitrergic neurotransmission.
Baccari
Maria Caterina
MC
Department of Physiological Sciences, University of Florence, Florence, Italy. mcaterina.baccari@unifi.it
Bani
Daniele
D
Calamai
Franco
F
D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology*; D006145:Guanethidine / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009287:Naphthyridines; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D000068797:Orexins; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D018679:Cholinergic Agonists; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D000068797:Orexins; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D010121:Oxytocin; D004246:Dimethylphenylpiperazinium Iodide; C015692:oxytocin, Asp(5)-; D014508:Urea; D002217:Carbachol; D010208:Papaverine; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester; D006145:Guanethidine