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

[摘要] References(37)Cited-By(7)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 norbinaltorphimine (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 μg per rat) into the lateral cerebroventricle (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 μg). The LV injection of naloxone benzoylhydrazone (a κ3-opioid receptor agonist, 100 μg) 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.

[学科分类] 药理学

[关键词] Gastric acid secretion;Opioid receptor;Dynorphin A-(1 – 17);Central injection