title: Pretreatment with SR48692 has different effects on central neurotensin-induced gastric mucosal defense and inhibition of gastric acid secretion in rats.
abstract: Neurotensin is a tridecapeptide present in the brain and gastrointestinal tract. Administration of neurotensin into the brain results in responses in the gastrointestinal tract, suggesting a role for neurotensin in the interrelationships that comprise the brain-gut axis. Intracerebroventricular (i.c.v.) administration of neurotensin protects the gastric mucosa against injury caused by cold water restraint (CWR) and also inhibits gastrin-stimulated gastric acid secretion. The hypothesis tested was that these two actions of neurotensin are mediated via its high-affinity receptor. Rats were given neurotensin (60 microgram, i.c.v.) prior to CWR or pylorus ligation after pretreatment with SR48692, a nonpeptide antagonist of the high-affinity neurotensin receptor (0.25 or 2.5 microgram, i.c.v., or 10, 100, or 500 microgram kg-1, i.p.). Neurotensin reduced cold water restraint (CWR)-induced gastric mucosal injury and inhibited gastrin-stimulated acid secretion. Pretreatment with SR48692 (2.5 microgram, i.c.v., or 100 microgram kg-1, i.p.) prior to CWR blocked neurotensin's protection of the gastric mucosa against injury. In contrast, pretreatment with 2.5 microgram SR48692, i.c.v., did not block neurotensin-induced inhibition of acid secretion, whereas 500 microgram kg-1, i.p., partially blocked the inhibition. SR48692 (2.5 microgram, i.c.v.) inhibited acid secretion, suggesting that SR48692 has agonist activity in this system. These results suggest that central neurotensin protects the gastric mucosa against CWR-induced injury via its high-affinity receptor. The receptor that mediates central neurotensin-induced inhibition of gastric acid secretion does not appear to be the high-affinity receptor since the neurotensin receptor antagonist SR48692, when given i.c.v., had agonist activity, inhibiting stimulated acid secretion. High-affinity neurotensin receptors in the periphery appear to play a role in inhibition of stimulated gastric acid secretion.
authors.affiliation: Division of General Surgery, Department of Surgery, The Pennsylvania State University College of Medicine, P.O. Box 850, Hershey, PA 17033, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Karinch
authors.forename: G L
authors.initials: GL
authors.lastname: Schmidt
authors.forename: G L
authors.initials: GL
authors.lastname: Kauffman
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003080:Cold Temperature; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D011708:Pylorus / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D000897:Anti-Ulcer Agents; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D009496:Neurotensin; D010418:Pentagastrin