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

Abstract

Acid secretion from isolated and enriched guinea-pig parietal cells stimulated by histamine and measured by the ¹⁴C-aminopyrine accumulation technique was enhanced by nanomolar concentrations of D-ala²-D-leu⁵-enkephalin (DADLE). This effect was blocked by naloxone. Naloxone inhibited histamine-stimulated acid secretion even in the absence of exogenous opioids. The effect of naloxone was stereospecific, i.e. (+)-naloxone was ineffective. The DADLE effect varied between different cell preparations and changed from stimulation to inhibition as the inhibitory effect of naloxone alone increased. Thus, an inverse relationship between the magnitude of inhibition by naloxone and enhancement by DADLE was observed. The data suggest that endogenous opioids modulate acid secretion in gastric muco-sal cells.

Intracellular Signalling and Regulation of Gastric Acid Secretion

“…However, in rat (Schepp & Ruoff, 1984) and human (Miederer et al 1986) parietal cells the effects of glucagon and histamine on adenylate cyclase activity were additive. Glucagon did not increase aminopyrine accumulation in rat parietal cells (Schepp & Ruoff, 1984 (Kromer, Schroder & Netz, 1984;Schepp, Schneider, Schusdziarra & Classen, 1986). The effects of these opioid peptides were blocked by (-)naloxone.…”

“…Opioid peptides? D-Ala2-D-leu5-enkephalin and met-enkephalin produced a small enhancement of histamine-stimulated aminopyrine accumulation in parietai cells from guinea-pig and rat (Kromer, Schroder & Netz, 1984;Schepp, Schneider, Schusdziarra & Classen, 1986). The effects of these opioid peptides were blocked by (-)naloxone.…”

Protection by Opioids against Gastric Lesions Caused by Necrotizing Agents

“…This might be an expression of the general distress (including marked re spiratory depression) manifested by the ani mals given these elevated doses of opioids; 20% of the rats died, in fact, with the com bined treatment of ulcerating solutions and opioids. However, bearing in mind the con tradictory literature on the effects of opioids even in the stomach [7][8][9][10], the possibility of a biphasic effect of opioids, linked to the size of dose, cannot be excluded.…”