[14C]-aminopyrine accumulation by isolated human parietal cells.
Gastric mucosal cells were isolated from resected fundic mucosa of peptic ulcer patients and used to determine H+ production by [14C]-aminopyrine (AP) uptake. H+ production was stimulated by histamine linearly for 40 min and in a concentration-dependent manner reaching a maximum of 228% of basal at 10(-4) mol/l histamine. This response was reduced by the histamine H2-receptor antagonist ranitidine (IC50 = 3 X 10(-6) mol/l). Pentagastrin and carbachol induced a small but significant increase at 10(-7) and 10(-4) mol/l, respectively. At low histamine concentrations the response to carbachol plus histamine was nearly additive. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) was a powerful stimulant of basal AP uptake but failed to augment the histamine effect. IBMX-induced AP uptake was reduced by ranitidine suggesting that, at least in part, the response to IBMX is mediated by release of endogenous histamine. Isopycnic centrifugation with Percoll resulted in fractions with 7 and 72% parietal cells, respectively. Basal AP uptake amounted to 203 cpm/10(6) cells in the parietal cell depleted fraction whereas in the enriched preparation the basal rate (4,787 cpm/10(6) cells) exceeded the uptake which was to be expected due to 10-fold parietal cell enrichment. When calculated as percentage of the basal H+ production the histamine-stimulated AP uptake was less in the enriched fraction than in the parietal cell depleted or in the nonfractionated preparation. Basal AP uptake was reduced by ranitidine more effectively in the enriched fraction suggesting background stimulation by endogenous histamine which might impair the response to exogenous stimulants. This functional evidence was paralleled by electron microscopical identification of mast cells copurified in the enriched parietal cell fraction.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000632:Aminopyrine / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000648:ultrastructure; D008875:Middle Aged; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000648:ultrastructure; D010418:Pentagastrin / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D000632:Aminopyrine; D006632:Histamine; D011899:Ranitidine; D002217:Carbachol; D010418:Pentagastrin; D015056:1-Methyl-3-isobutylxanthine