Role of brain neurotransmitters on neurotensin-induced gastric cytoprotection.
We have reported previously that intracisternal (IC) administration of neurotensin (NT) prevents stress-induced gastric ulcers in rats. This effect of NT appears to be mediated by the central nervous system because peripheral (IV) NT is totally ineffective. The present study sought to clarify the central mechanism of the cytoprotective effect of NT by utilizing pharmacological treatments which alter the function of brain neurotransmitter systems. Pretreatment with intracerebroventricular (ICV) administration of agonists and antagonists of acetylcholine (ACh), gamma-aminobutyric acid (GABA), and serotonin (5-HT) receptors or with an anti-opiate (naloxone) agent did not significantly alter NT-induced cytoprotection. However, pretreatment with ICV haloperidol, a dopamine (DA) receptor antagonist, totally blocked NT's cytoprotective effect. In addition, pretreatment with methylphenidate, a DA receptor agonist, produced cytoprotection similar to IC NT. These data indicate that NT-induced cytoprotection is not mediated by 5-HT, GABA, ACh (muscarinic) receptors, or endogenous opiate systems, but suggest interactions between brain DA systems and NT.
Hernandez
D E
DE
Stanley
D A
DA
Melvin
J A
JA
Prange
A J
AJ
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002946:Cisterna Magna; D003080:Cold Temperature; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007267:Injections; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D011957:Receptors, Opioid / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000517:prevention & control*; D013315:Stress, Psychological / Q000503:physiopathology
D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D009496:Neurotensin; D006220:Haloperidol