Jpn. J. Pharmacol. 87 (1), 14-20 (2001)

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

Satomi Ishihara, Shizuko Tsuchiya, Syunji Horie, Toshihiko Murayama* and Kazuo Watanabe

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan

*Corresponding author. FAX: +81-43-290-3021, E-mail:

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 k-opioid receptors stimulated gastric acid secretion in rats, and the secretion by the agonists was inhibited by norbinaltorphimine (an antagonist of k-opioid receptor). In the present study, we investigated the effect of dynorphin A-(1 - 17), an endogenous ligand of k-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 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 mg) 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 mg). The LV injection of naloxone benzoylhydrazone (a k3-opioid receptor agonist, 100 mg) also stimulated the secretion in norbinaltorphimine-sensitive manner. These findings showed that both an endogenous ligand dynorphin A-(1 - 17) and a synthetic k3-opioid receptor agonist stimulated gastric acid secretion via k-opioid receptors in the CNS of rats in vivo.

Keywords: Gastric acid secretion, Opioid receptor, Dynorphin A-(1 - 17), Central injection
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