Synthesis of nitric oxide in the dorsal motor nucleus of the vagus mediates the inhibition of gastric acid secretion by central bombesin.
1. Central administration of bombesin inhibits gastric acid production independently of the centrally or peripherally-acting stimuli employed. This study evaluates the role and location of the cerebral nitric oxide (NO) implicated in the inhibitory effect of central bombesin on in vivo rat gastric acid secretion, as induced by distension with 15 cm H2O, insulin (0.75 u.i. kg-1 i.p.) TRH (1.2 microg kg-1, i.c.) or pentagastrin (100 microg kg-1, i.p.). 2. The acid-inhibitory effect of i.c. bombesin (40 ng kg-1) was prevented by prior administration of L-NAME (80 microg kg-1) in the dorsal motor nucleus of the vagus (DMN). This dose of L-NAME when administered into the nucleus of the tractus solitarious (NTS) did not influence the effects of bombesin. Administration of L-arginine (400 microg kg-1) into the DMN restored the acid-inhibitory effect of i.c. bombesin in animals treated with L-NAME. 3. Microinjection of bombesin (12 ng kg-1) into the paraventricular nucleus of the hypothalamus (PvN) inhibits acid secretion stimulated by pentagastrin. This inhibitory effect was prevented by a previous injection of L-NAME (80 microg kg-1) into the DMN. 4. The release of NO in the DMN following i.c. administration of bombesin was confirmed by in vivo electrochemical detection. 5. Administration by microdialysis in the DMN of the NO-donor SNAP (25 mM in 1.5 microl min-1) into the DMN inhibits pentagastrin-stimulated gastric acid secretion. 6. The present study suggests that nNOS-containing neurons in the DMN have an inhibitory role in the control of gastric acid responses.
Beltrán
B
B
Department of Pharmacology, Faculty of Medicine, University of Valencia, Avd. Blasco Ibañez 15, 46010 Valencia, Spain.
Barrachina
M D
MD
Méndez
A
A
Quintero
E
E
Esplugues
J V
JV
D000818:Animals; D001839:Bombesin / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D010286:Paraventricular Hypothalamic Nucleus; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010418:Pentagastrin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D013973:Thyrotropin-Releasing Hormone; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D010418:Pentagastrin; D010396:Penicillamine; D001839:Bombesin; D019331:NG-Nitroarginine Methyl Ester