Inhibition of epidermal growth factor receptor activation by tyrosine kinase inhibitor enhances in vivo histamine stimulated gastric acid secretion in the rat

Abstract

8s (03-100 mnobkg .h 1) was initiated. Microdialysate samples were collected ever}. hour for 4 h The amoum of histamine mobilized was expressed as the integrated increment of microdialysate histamine. 2) The effect of continuons infusion of devazepide (200 ~g.kg'l-h , sc) on CCK-induced histamine mobilization was also ins, estigated, 3) and tile microdialysate somatostatin concentration was assayed as well. RESULTS: 1) Gastrin and CCK promptly raised the microdialysate histamine concentration m a dose-dependent manner. With both hormones the histamine concentration reached maxmium wit fun the first hour; this elevation was sustained for 4 h with gastrin but not with CCK. The ED~) value for gastrin (histamine mobilized during 4D was 0.8 nmobkg*.h and for CCK 4.8 nmol.kgl.h . 2) Continuous infusion of devazepide enhanced the CCK-induced histamine nrobdization. With depazepide, the response to CCK remained at a plateau tbr 6 h Devazepide alone did not affect the microdialysate histamine concentration. 3) The microdialysate sotnatnstatin concentration increased slowly in response to CCK, reaching maximum 2h after start of the infusion, and remaining at this level for 4h. Depazepide inhibited the CCK-evoked sumatostatin secretion. CONCLUSIONS: In vivo, gastrin was more effective than CCK in mobilizing ECL-cell histamitre despite the fact that both hormones stimulate the CCK~ receptor on the ECL cells. Conceivably CCK, unlike gastrin, stimulates the CCKt receptor of the D cell to mobilize somatostatin, which inhibits ECL<ell histamine secretion.