ABSTRACT
The stimulation of the oxyntic cell by gastric secretagogues is associated to the activation of oxidative metabolism. The mechanisms of this activation are not exactly known. In the present work, we investigated the possible direct effect of Ca2+ on both oxoglutarate oxidation in rabbit gastric glands and oxoglutarate dehydrogenase activity (OGDH) is isolated gastric mitochondria. Both carbachol and Ca2+ ionophores +(A23187 and ionomycin) significantly stimulated oxoglutarate oxidation in a dose-dependent manner. This effect was only observed in the presence of low substrate concentrations. BAPTA-AM, an intracellular calcium chelator, significantly inhibited the rate of oxoglutarate oxidation. OGDH activity was stimulated by physiological concentrations of Ca2+ in a dose-depentent manner. This effect was reduced by ruthenium red, an inhibitor of mitochondrial Ca2+ uptake, and it was additionally increased by spermine, a stimulant of Ca2+ influx to the mitochondria. Results support the hypothesis that Ca2+ plays a direct role in the activation of oxidative metabolism in the oxyntic cell
Subject(s)
Animals , Rabbits , Ketoglutaric Acids/metabolism , Calcium/physiology , Gastric Mucosa/metabolism , Oxidoreductases/metabolism , Carbachol/pharmacology , Parietal Cells, Gastric , Parietal Cells, Gastric/metabolism , Ionophores/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Gastric Mucosa , Gastric Mucosa/enzymologyABSTRACT
The stimulation of oxyntic cell by gastric secretagogues is associated to the activation of oxidative metabolism. The mechanisms of this activation are not exactly known. In the present work, we investigated the possible direct effect of Ca2+ on both oxoglutarate oxidation in rabbit gastric glands and oxoglutarate dehydrogenase activity (OGDH) in isolated gastric mitochondria. Both carbachol and Ca2+ ionophores (A23187 and ionomycin) significantly stimulated oxoglutarate oxidation in a dose-dependent manner. This effect was only observed in the presence of low substrate concentrations. APTA-AM, an intracellular calcium chelator, significantly inhibited the rate of oxoglutarate oxidation. OGDH activity was stimulated by physiological concentrations of Ca2+ in a dose-dependent manner. This effect was reduced by ruthenium red, an inhibitor of mitochondrial Ca2+ uptake, and it was additionally increased by spermine, a stimulant of Ca2+ influx to the mitochondria. The results support the hypothesis that Ca2+ plays a direct role in the activation of oxidative metabolism in the oxyntic cell