Gastric Acid Secretion by Central Injection of Dynorphin A-(1 - 17), an Endogenous Ligand of κ-Opioid Receptor, in Urethane-Anesthetized Rats

Abstract

Gastric acid secretion has been proposed to be regulated by opioid receptors in the central nervous system (CNS). Previously, we reported that central injection of synthetic agonists of κ-opioid receptors stimulated gastric acid secretion in rats, and the secretion by the agonists was inhibited by norbinaltor-phimine (an antagonist of κ-opioid receptor). In the present study, we investigated the effect of dynorphin A-(1 - 17), an endogenous ligand of κ-opioid receptor on the gastric acid secretion in the perfused stomach of urethane-anesthetized rats. Injection of dynorphin A-(1 - 17) (0.1 - 1 mg per rat) into the lateral cerebro-ventricle (LV) stimulated the secretion in a dose-dependent manner. The effect of dynorphin A-(1 - 17) was almost completely inhibited by the LV injection of norbinaltorphimine (10 μg) and in vagotomized rats. Although some studies of dynorphin A-(1 - 17) after central injection showed non-opioid effects such as the involvement of N-methyl-D-aspartate (NMDA) receptor, the effect of dynorphin A-(1 - 17) was not inhibited by a selective antagonist of the NMDA receptor ((±)-3-(2-carboxypiperazin-4-yl)-1-propylphosphonic acid, 10 μ g). The LV injection of naloxone benzoylhydrazone (a κ3-opioid receptor agonist, 100 μ g) also stimulated the secretion in norbinaltorphimine-sensitive manner. These findings showed that both an endogenous ligand dynorphin A-(1 - 17) and a synthetic κ3-opioid receptor agonist stimulated gastric acid secretion via κ-opioid receptors in the CNS of rats in vivo.