Gastric acid secretion by central injection of dynorphin A-(1-17), an endogenous ligand of kappa-opioid receptor, in urethane-anesthetized rats.
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.
Ishihara
S
S
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
Tsuchiya
S
S
Horie
S
S
Murayama
T
T
Watanabe
K
K
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
D018686:Anesthetics, Intravenous; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D014520:Urethane; D004399:Dynorphins