title: Gastric acid secretion by central injection of dynorphin A-(1-17), an endogenous ligand of kappa-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 kappa-opioid receptors stimulated gastric acid secretion in rats, and the secretion by the agonists was inhibited by norbinaltorphimine (an antagonist of kappa-opioid receptor). In the present study, we investigated the effect of dynorphin A-(1-17), an endogenous ligand of kappa-opioid receptor on the gastric acid secretion in the perfused stomach of urethane-anesthetized rats. Injection of dynorphin A-(1-17) (0.1-1 microg 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 microg) 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 microg). The LV injection of naloxone benzoylhydrazone (a kappa3-opioid receptor agonist, 100 microg) also stimulated the secretion in norbinaltorphimine-sensitive manner. These findings showed that both an endogenous ligand dynorphin A-(1-17) and a synthetic kappa3-opioid receptor agonist stimulated gastric acid secretion via kappa-opioid receptors in the CNS of rats in vivo.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishihara
authors.forename: S
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: S
authors.initials: S
authors.lastname: Horie
authors.forename: T
authors.initials: T
authors.lastname: Murayama
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects; D014520:Urethane / Q000008:administration & dosage
chemical_list: D018686:Anesthetics, Intravenous; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D014520:Urethane; D004399:Dynorphins