Modulation of Acid Secretion from Enriched Guinea Pig Parietal Cells by Opioid Receptors

Abstract

Membrane fragments of isolated cells from guinea pig gastric mucosa, enriched to 65% parietal cells, bind with high affinity the opioid peptide ³H-D-Ala²-D-Leu⁵-enkephalin (³H-DADLE). Binding was saturable and reversible. Scatchard analysis revealed a second binding site with low affinity but high capacity. Acid secretion by isolated, enriched parietal cells was determined by means of ¹⁴C-aminopyrine uptake. Basal acid secretion was not influenced by DADLE but that stimulated by histamine was further augmented by the enkephalin analog. This potentiating effect was prevented by the opioid antagonist naloxone. The present data provide for the first time evidence that gastric acid secretion is modulated by an opioid mechanism probably located on the parietal cell.

Stereospecific Inhibition by Naloxone of Histamine-Stimulated Acid Secretion in Isolated Guinea Pig Parietal Cells

“…The present investigation confirms and extends previous data from this laboratory showing that the opioid peptide DADLE [25] enhances histamine-stimulated acid secre tion in isolated guinea-pig parietal cells in a naloxone-blockable fashion [10]. DADLE, which is relatively resistant to enzymatic deg radation [19], produces an effect which, al though small, is observed even at nanomolar concentrations.…”

“…It is still a matter of debate whether opioids have an effect on gastric acid secre tion and if so, whether they stimulate or inhibit, and whether the effect is elicited in the gastric mucosa or centrally [3,4,6,8,9,11,12,14,17,21,23], In a previous paper [10], we have demonstrated for the first time that the opioid peptide D-ala2-Z)-leu5-enkephalin (DADLE) [25] enhanced acid secre tion stimulated by histamine in isolated and enriched guinea pig parietal cells. The effect was blocked by the competitive opioid antag onist naloxone, suggesting a specific effect on opioid receptors.…”

Gastric Secretion and Mucosal Lesions in Morphine-Dependent Rats

“…For example, Kromeret al [15] reported that opioids increased, while naloxone de creased. histamine-stimulated acid secretion by isolated guinea pig parietal cells.…”

Endogenous Opioids, the Enteric Nervous System and Gut Motility

“…It was regarded as a specific tool for proving opioid functions by blocking opioid receptors and, thus, un masking endogenous opioid actions. During the following years, however, it was recog nized that opioid peptides intrinsic to the GI tract physiologically modulate reflex peri stalsis in an inhibitory fashion [15] and acid secretion by isolated gastric parietal cells in an excitatory fashion [16], thus explaining the opposite effects of naloxone alone.…”