Stimulatory effects of centrally injected kainate and N-methyl-D-aspartate on gastric acid secretion in anesthetized rats.
The effects of N-methyl-D-aspartate (NMDA), kainate and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), ionotropic glutamate agonists, on gastric acid secretion were investigated in the continuously perfused stomach of anesthetized rats. The lateral ventricular (LV) injection of kainate (0.01-1 microg) or NMDA (0.3-3 microg) dose-dependently stimulated gastric acid secretion. AMPA (3-10 microg) also stimulated gastric acid secretion but the effect was very weak. Repeated injections of kainate (0.1 microg) or NMDA (1 microg), at least twice, stimulated gastric acid secretion to a similar degree. The effect of kainate (0.1 microg) was blocked by the kainate receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione disodium (3 microg, LV) and D-gamma-glutamylaminomethanesulfonic acid (30 microg, LV), but not by NMDA receptor antagonists. The effect of NMDA (10 microg) was blocked by (+/-)-3-(2-carboxypiperazin-4-yl)-1-propylphosphonic acid (10 microg, LV), a competitive NMDA receptor antagonist, and (+)-5-methyl-10,11-dihydro-5H-dibenzocyclo-hepten-5,10-imine hydrogen maleate (10 microg, LV), a non-competitive NMDA receptor antagonist, but not by kainate receptor antagonists. Moreover, the gastric acid secretion stimulated by kainate and NMDA were completely blocked by systemic atropine injection (1 mg/kg, i.v.) and vagotomy. These findings suggest that kainate and NMDA receptor mechanisms are independently involved in the central nervous system to control gastric acid secretion through vagus cholinergic activation.
Tsuchiya
S
S
Laboratory of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Chiba University, 263-8522, Chiba, Japan. stsuchi@p.chiba-u.ac.jp
Horie
S
S
Yano
S
S
Watanabe
K
K
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000294:innervation* / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000109:Acetylcholine; D001285:Atropine; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D018727:Muscarinic Antagonists; D016202:N-Methylaspartate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid