Effects of pentagastrin and carbachol on the gastric histamine level in alpha-fluoromethylhistidine-treated mice and rats.
The gastric mucosal histamine level in mice increased by about 80% and 100% after fasting for 24 and 48 h, respectively. In non-fasted mice, alpha-fluoromethylhistidine (alpha-FMH), a specific histidine decarboxylase inhibitor, significantly decreased the histamine level, the reduction amounting to 35% and 49%, 2 h and 4 h after treatment, respectively. In mice fasted for 24 h, a significant decrease of 42% was observed 4 h after treatment. However, in mice fasted for 48 h, no significant decrease was seen even 4 h after alpha-FMH treatment. Therefore, the histamine-releasing effect of re-feeding and drugs on the gastric mucosa was examined in vivo, using animals fasted for 48 h and subsequently treated with alpha-FMH. Food given simultaneously with alpha-FMH to 48-h fasted mice significantly decreased the histamine level 4 h later. Pentagastrin and carbachol administered alone (0.25-2.0 mg/kg, i.p.) had no significant effect on the histamine level. However, the combined treatment with these drugs significantly decreased the histamine level. In rats fasted for 48 h and treated with alpha-FMH, pentagastrin (0.25 and 0.5 mg/kg, i.p.) but not carbachol (0.125-0.5 mg/kg, i.p.) caused a significant decrease in the mucosal histamine level. In contrast to mice, the effect of the combined treatment with pentagastrin and carbachol was not synergistic in rats. These findings suggest that gastrin acts synergistically with acetylcholine in the histamine release from the gastric mucosa in mice, whereas such synergism may not occur in rats.
Department of Pharmacology, Okayama University Medical School, Japan.
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Koyama
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Oishi
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Saeki
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006639:Histidine / Q000031:analogs & derivatives*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010418:Pentagastrin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects
D008762:Methylhistidines; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D002217:Carbachol; D006640:Histidine Decarboxylase; D010418:Pentagastrin