Influence of opiates on alkali secretion by amphibian gastric and duodenal mucosa in vitro

Abstract

Experiments were performed to study the effects of opiates on gastric and duodenal alkali secretion in amphibian mucosa in vitro. Alkali secretion by fundic mucosa of Rana temporaria, or antral mucosa of Rana catesbeiana, was unaffected by morphine, methionine-enkephalin and leucine-enkephalin, two enkephalin analogues, or the opiate antagonist naloxone. Acid secretion by fundic mucosa in vitro was not influenced by 10−5 and 10−4 M morphine, or by 10−7 to 10−5 M naloxone. However, duodenal alkali secretion in Rana catesbeiana was stimulated by opiates while the electrical potential difference was unaffected. Morphine stimulated secretion, maximally at 10−5 M, by 33% over basal values, 30 min after exposure to the drug, whereas the maximal response to methionine-enkephalin occurred at 10−6 M and was obvious within the first 15 min after administration. The effects of these opiates were prevented by pretreatment with naloxone or with the more specific opiate receptor antagonist ICI 154129. The response to morphine was inhibited when bicarbonate in the nutrient-side solution was replaced by the impermeant anion HEPES or by removal of chloride from the bathing media. Furosemide (10−3 M) also inhibited the response of duodenal mucosa to morphine. The nerve-blocker tetrodotoxin (10−7 M) prevented the morphine-induced response. These data suggest that opiates can stimulate duodenal alkali secretion, probably by activating an electrically neutral Cl−/HCO3− exchange. It seems likely that the effect of opiates is mediated by a neurologic intermediary, and the results suggest the possibility that duodenal alkali secretion may be under some neurologic control.