Failure of 16-16-Dimethyl-Prostaglandin E2 to Stimulate Alkaline Secretion in the Isolated Amphibian Gastric Mucosa

It has been suggested that the gastric cytoprotective action of prostaglandins is mediated by stimulation of alkaline secretion. We tested the effect of 16-16-dimethyl-prostaglandin E2 (16-16D) in isolated amphibian gastric mucosa (Rana Catesbeiana) by measuring alkaline secretion, potential difference, resistance, and short circuit current of the chambered tissues gassed with 100% O2 on the secretory side and 95% O2-5% CO2 on the nutrient side. Production of CO2 was also measured during uniform gassing with 100% O2. 16-16D concentrations of 10−6 M, 2.85 × 10−6 M, 5 × 10−6 M, and 10−5 M in the nutrient solution did not affect a basal alkaline secretion of ~0.22 μeq/cm2/hr in metiamide-inhibited fundic mucosa. Production of CO2 on the secretory side of actively secreting mucosae was not changed by 16-16D, 2.85 × 10−6 M. A basal alkaline secretion of ~0.25 μeq/cm2/hr in antral mucosa was not altered by 16-16D, 10−6 M. Change of the nutrient solution regularly and reliably increased titratable alkalinity on the mucosal side even when no 16-16D was present in the new nutrient solution. Since stimulation of apparent alkaline secretion occurred only when the nutrient solution was changed, as in the experiments of other investigators, it is reasonable to assume that such an increase in alkaline secretion is an artifact caused by changing the equilibrium between HCO3− and CO2 in the secretory solution, a phenomenon easily demonstrable when a tissue is gassed with 100% O2 on the secretory side and 95% O2-5% CO2 on the nutrient. We conclude that stimulation of alkaline secretion by 16-16D in amphibian gastric mucosa does not occur and is therefore not the mechanism by which cytoprotection is mediated in this species.