Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa.
The stimulation of acid secretion by gastrin may in the rat be explained solely by gastrin-induced histamine release. This study was done to examine whether histamine could mediate the general trophic effect of gastrin on the oxyntic mucosa, by using a long-acting selective histamine-1 antagonist (astemizole) alone or with omeprazole-induced hypergastrinaemia for 90 days in female Sprague-Dawley rats. At day 90, isolated vascularly perfused rat stomachs were prepared to study maximal gastrin- and histamine-stimulated acid and pepsinogen outputs and maximal gastrin-stimulated histamine release. Oxyntic mucosa morphometry, mucosal histamine and pepsinogen contents, and plasma gastrin and histamine levels were also determined. For the first time, omeprazole has been found to inhibit gastric emptying and to increase plasma histamine. As compared with controls, astemizole alone did not influence plasma gastrin, increased plasma histamine in only some rats, and gave a slight increase in all other variables. Together with omeprazole, it further increased variables already stimulated by omeprazole. Thus, mucosal thickness, histamine concentration, and chief-cell density in oxyntic mucosa were significantly higher in astemizole/omeprazole-treated rats than in omeprazole-treated rats. Gastrin-stimulated histamine release was increased in both astemizole- and omeprazole-treated rats. For all rats plasma histamine was significantly correlated with plasma gastrin and with numerical fundic argyrophil cell density. In conclusion, the present study confirms the trophic effect of gastrin and shows a slight trophic effect of astemizole on the oxyntic mucosa. It also shows that plasma histamine may reflect the argyrophil cell density in the oxyntic mucosa and that omeprazole inhibits gastric emptying.
Waldum
H L
HL
Institute of Cancer Research, University Hospital, Trondheim, Norway.
Lehy
T
T
Brenna
E
E
Sandvik
A K
AK
Petersen
H
H
Søgnen
B S
BS
Bonfils
S
S
Lewin
M J
MJ
D000818:Animals; D016589:Astemizole; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D002452:Cell Count; D004359:Drug Therapy, Combination; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005755:Gastrins / Q000097:blood; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006636:Histamine Release; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains
D001562:Benzimidazoles; D005755:Gastrins; D006634:Histamine H1 Antagonists; D016589:Astemizole; D009853:Omeprazole