Mesolimbic dopamine mediates gastric mucosal protection by central neurotensin

1991 ◽  
Vol 260 (1) ◽  
pp. G34-G38 ◽  
Author(s):  
L. P. Xing ◽  
C. Balaban ◽  
J. Seaton ◽  
J. Washington ◽  
G. Kauffman
Keyword(s):  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Acid Secretion ◽  
Lateral Ventricle ◽  
Cold Water ◽  
Mucosal Injury ◽  
Mucosal Protection ◽  
Minimal Effective Dose ◽  
Gastric Mucosal Protection ◽  
6 Hydroxydopamine

Bilateral microinjection (1.0 microliter/side) of neurotensin (NT; 0.3, 1.5, and 3.0 micrograms/side) into the nucleus accumbens (NACB) and ventral tegmental area (VTA) but not in substantia nigra and striatum reduced gastric mucosal injury produced by 2 h of cold-water restraint (CWR). The minimal effective dose for NT-induced protection was 10-100 times lower when administered directly into NACB than into the lateral ventricle. These effects were blocked by pretreatment with the dopamine (DA) receptor antagonist, haloperidol (Hal; 0.5 microgram/side) given directly into NACB. Injection of 6-hydroxydopamine into VTA depleted endogenous DA and inhibited gastric mucosal protection against CWR-induced injury afforded by NT pretreatment. NT, given into either VTA and NACB, inhibited pentagastrin-stimulated gastric acid secretion. These results suggest that VTA and NACB, which represent the mesolimbic DA system, are important locations for interaction between NT and DA receptors to produce gastric mucosal protection against CWR-induced injury.

Effect of neurotensin on regional cerebral glucose utilization in cold water-restrained rats

1990 ◽  
Vol 258 (4) ◽  
pp. G591-G595
Author(s):  
L. P. Xing ◽  
J. C. King ◽  
R. M. Bryan ◽  
G. L. Kauffman
Keyword(s):  
Nucleus Accumbens ◽  
Glucose Utilization ◽  
Cold Water ◽  
Mucosal Injury ◽  
Ulcer Formation ◽  
Neuronal Function ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Or Groups ◽  
Nuclear Group

Neurotensin (NT), given intracerebroventricularly (icv), attenuates cold water restraint (CWR)-induced gastric mucosal injury; however, it is not clear which brain nuclear group or groups are involved. These studies tested the hypothesis that neuronal function, as measured by regional cerebral metabolic rate for glucose (rCMRGlc), is altered by icv NT with or without CWR. CWR resulted in a reduced global glucose utilization of 72 and 65% in control and NT-treated rats, respectively. NT, given icv, protected against ulcer formation induced by CWR. In those rats given NT icv, rCMRGlc was elevated significantly in amygdala, nucleus accumbens, substantia nigra, tuberculum olfactrium, hypothalamus, and cerebellum compared with CWR rats without NT pretreatment. This rCMRGlc increase was observed in both unstressed and stressed rats given NT icv in the nucleus accumbens and amygdala. These observations suggest that the nucleus accumbens and amygdala, both components of the mesolimbic dopamine system, are involved in the central action of NT on the gastric mucosa.

Gastric mucosal protection against ethanol by EP2 and EP4 signaling through the inhibition of leukotriene C4 production

2008 ◽  
Vol 294 (1) ◽  
pp. G80-G87 ◽  
Author(s):  
Youichiro Hattori ◽  
Takashi Ohno ◽  
Takako Ae ◽  
Takeo Saeki ◽  
Katsuharu Arai ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Protective Action ◽  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Ethanol Administration ◽  
Receptor Subtypes ◽  
Receptor Signaling ◽  
Mucosal Protection ◽  
Anesthetized Rats ◽  
Gastric Mucosal Protection

Prostaglandin (PG)E derivatives are widely used for treating gastric mucosal injury. PGE receptors are classified into four subtypes, EP1, EP2, EP3, and EP4. We have tested which EP receptor subtypes participate in gastric mucosal protection against ethanol-induced gastric mucosal injury and clarified the mechanisms of such protection. The gastric mucosa of anesthetized rats was perfused at 2 ml/min with physiological saline, agonists for EP1, EP2, EP3, and EP4, or 50% ethanol, using a constant-rate pump connected to a cannula placed in the esophagus. The gastric microcirculation of the mucosal base of anesthetized rats was observed by transillumination through a window made by removal of the adventitia and muscularis externa. PGE2 and subtype-specific EP agonists were applied to the muscularis mucosae at the window. Application of 50% ethanol dilated the mucosal arterioles and constricted the collecting venules. Collecting venule constriction by ethanol was completely inhibited by PGE2 and by EP2 and EP4 agonists (100 nM) but not by an EP1 or an EP3 agonist. Ethanol-induced mucosal injury was also inhibited by EP2 and EP4 agonists. When leukotriene (LT)C4 levels in the perfusate of the gastric mucosa were determined by ELISA, intragastric ethanol administration elevated the LTC4 levels sixfold from the basal levels. These elevated levels were significantly (60%) reduced by both EP2 and EP4 agonists but not by other EP agonists. Since LTC4 application at the window constricted collecting venules strongly, and an LTC antagonist reduced ethanol-induced mucosal injury, reductions in LTC4 generation in response to EP2 and EP4 receptor signaling may be relevant to the protective action of PGE2. The present results indicate that EP2 and EP4 receptor signaling inhibits ethanol-induced gastric mucosal injury through cancellation of collecting venule constriction by reducing LTC4 production.

Nonprotein sulfhydryl compounds in canine gastric mucosa: effects of PGE2 and ethanol

1985 ◽  
Vol 249 (1) ◽  
pp. G137-G144 ◽  
Author(s):  
T. A. Miller ◽  
D. Li ◽  
Y. J. Kuo ◽  
K. L. Schmidt ◽  
L. L. Shanbour
Keyword(s):  
Gastric Mucosa ◽  
Low Dose ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
High Dose ◽  
Mucosal Protection ◽  
Gastric Mucosal Protection ◽  
Sulfhydryl Compounds ◽  
Mild Irritants

By use of an in vivo canine chambered stomach preparation in which the gastric mucosa was partitioned into two equal halves, the effect of topical 16,16-dimethyl PGE2 (DMPGE2) (1 microgram/ml of perfusate) and 8% and 40% ethanol on tissue levels of nonprotein sulfhydryl compounds was assessed. Both DMPGE2 and 8% ethanol significantly increased (P less than 0.005) mucosal levels of nonprotein sulfhydryls when compared with corresponding mucosa bathed with saline alone. In contrast, mucosa bathed with 40% ethanol showed significantly decreased levels. If mucosa was bathed with DMPGE2 or 8% ethanol prior to exposing the stomach to 40% ethanol, this depletion in sulfhydryl compounds was not observed. Since other experimental observations have shown that exogenously administered prostaglandins and mild irritants (such as low-dose alcohol) can prevent gastric mucosal damage by necrotizing agents (such as high-dose alcohol), our findings are consistent with the hypothesis that nonprotein sulfhydryls may play a role in mediating gastric mucosal protection.

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