Naturally occurring opioid peptides modulate H⁺-production by isolated rat parietal cells

The rationale for the present study was to determine the effects of naturally occurring opioid peptides on H⁺-production by isolated rat parietal cells as indirectly measured by [¹⁴C]-aminopyrine uptake. In crude preparations (18 to 25% parietal cells) and in enriched (80 to 90%) parietal cell fractions stimulation by submaximal histamine- or dibutyryl cAMP-concentrations (10^-6-10^-4 mol/l) was augmented by 20-30% in the presence of methionine-enkephalin (Met-Enk) and Met-Enk Arg⁶Phe⁷ (10^-7 to 10^-5 mol/l). This augmentation was blocked by the opiate receptor antagonist (-)naloxone (10^-6 mol/l) suggesting specificity of the action of Met-Enk and Met-Enk Arg⁶Phe⁷. At 10^-6 mol/l (-)naloxone did not exert nonspecific toxic effects. Yet, even in the absence of exogenous opioids, histamine-induced H⁴-production was inhibited by 3×10^-5 or 10^-4 mol/l (-)naloxone. Since similar inhibition occurred with (+)naloxone, an inactive stereoisomer which does not interact with opiate receptors, effects of (-)naloxone at concentrations above 10^-5 mol/l must be considered nonspecific. We conclude that Met-Enk and Met-Enk Arg⁶Phe⁷ have no effect on basal, but augment stimulated H⁺-production by a direct effect on the parietal cells. At nontoxic concentrations (-)naloxone antagonizes this augmentation indicating that it is mediated by specific opiate receptors on the parietal cells.