Gastric acid secretion stimulated by centrally injected nociceptin in urethane-anesthetized rats.
Nociceptin is a preferred endogenous ligand for the orphan opioid receptor-like 1 (ORL1) receptor. Central administration of nociceptin showed various pharmacological effects on analgesia, cardiovascular and renal responses, food intake, and so on. In the present study, we investigated the effect of nociceptin injected into the central nervous system (CNS) on gastric acid secretion in the perfused stomach of urethane-anesthetized rats. Injection of nociceptin (0.55-5.52 nmol per rat) into the fourth cerebroventricle stimulated gastric acid secretion and the secretion was inhibited in atropine-treated (1 mg/kg, i.v.) and vagotomized rats. The secretion induced by nociceptin (1.65 nmol) was not inhibited by the central injection of naloxone (275 nmol, a non-selective antagonist of opioid receptors). The secretion was significantly inhibited by the central injection of [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) ([F/G]nociceptin-(1-13), 0.21 nmol, an antagonist of ORL1 receptor), although [F/G]nociceptin-(1-13) alone at higher doses (2.10 and 7.31 nmol) markedly stimulated gastric acid secretion. In the 0-40 min period, the secretion induced by nociceptin was inhibited at least partially by CompB (68.8 nmol, a nonpeptidic antagonist of ORL1 receptor). Injection of nociceptin (5.52 nmol) into the lateral cerebroventricle also stimulated the secretion. Injection of nociceptin did not modify gastric acid secretion stimulated by 2-deoxy-D-glucose (200 mg/kg, i.v.). In conclusion, nociceptin injected into the CNS stimulated gastric acid secretion in rats via the ORL1 receptors and through mechanisms involving the vagus nerve.
Ishihara
Satomi
S
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
Minowa
Sachie
S
Tsuchiya
Shizuko
S
Horie
Syunji
S
Watanabe
Kazuo
K
Murayama
Toshihiko
T
D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists; D013270:Stomach / Q000187:drug effects; D013997:Time Factors; D014520:Urethane / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000494:pharmacology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018686:Anesthetics, Intravenous; D001285:Atropine; D003847:Deoxyglucose; D009270:Naloxone; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D014520:Urethane; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C439964:nociceptin (1-13) amide; C000722285:Oprl1 protein, rat