Effect of gamma-aminobutyric and gamma-hydroxybutyric acids on rate of14C-leucine incorporation into proteins of the gastric mucosa and hypothalamus

Mirzoyan, S. Å.; Tatevosyan, A. T.; Gevorkyan, G. A.

doi:10.1007/bf00830391

Cited by 2 publications

(2 citation statements)

References 3 publications

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“…Thus, GABA may be responsible for one or more of the reported gastric mucosal protection mechanisms mediated by mucosal GABA A ‐receptors [10]. The protective mechanisms might include an increase in the synthesis and ATP content of phosporylated gastric proteins [17,18]. On the other hand, GABA may enhance mucus secretion in the stomach [19].…”

Section: Discussionmentioning

confidence: 99%

Benzodiazepines protect against ethanol‐induced gastric mucosal damage in vitro*

Hummadi

Najim

Farjou

2001

Fundamemntal Clinical Pharma

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The protective effects of drugs acting at the benzodiazepine receptors against ethanol-induced gastric damage were investigated using a newly developed in vitro model of the ethanol-induced gastric damage. The rat stomachs were isolated from the whole animal and kept in Kreb's solution at 37 degrees C. Gastric damage was induced by administration of 1 mL of 50% V/V ethanol into the isolated rat stomach. Administration of the benzodiazepine agonist, clonazepam (25, 50, 100 microg), or the partial benzodiazepine inverse agonist Ro15-4513 (50 or 100 microg), significantly protected against ethanol-induced gastric damage when these agents were administered 15 min before ethanol. The protective effects of these drugs were blocked by the benzodiazepine receptor antagonist flumazenil (200-400 microg). Flumazenil alone was found to aggravate ethanol-induced gastric damage (200-400 microg). The results of this study give evidence for the involvement of central-type benzodiazepine receptors located in the stomach in the protective action of benzodiazepines against ethanol-induced gastric damage.

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Section: Discussionmentioning

confidence: 99%

Benzodiazepines protect against ethanol‐induced gastric mucosal damage in vitro*

Hummadi

Najim

Farjou

2001

Fundamemntal Clinical Pharma

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“…Thus, GABA may be responsible for one or more of the reported gastric mucosal protective mechanisms mediated by the mucosal GABA A receptor 3–5,12 , 24 . This effect may be related to a GABA‐induced increase in the synthesis and ATP content of phosphorylated gastric proteins, and consumption in the gastric wall and increased resistance of the gastric mucosa to the action of proteolytic enzymes 28,29 and/or to a GABA‐evoked enhancement of mucus secretion in the stomach, as reported by Lloyd et al 30 . However, it is unlikely that BZ protect the gastric mucosa through a GABA‐evoked enhancement of mucus secretion because ethanol can easily penetrate the mucus barrier 30…”

Section: Discussionmentioning

confidence: 99%

Drugs acting at the GABA_A receptor attenuate ethanol‐induced gastric mucosal damage *in vitro**

Najim

Saaed

2003

Clin Exp Pharma Physio

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1. Benzodiazepines (BZ) have been reported to protect against ethanol-induced gastric damage in rats in both in vivo and in vitro models. However, the effects of some drugs in the new in vitro model do not agree with results reported previously in in vivo studies. 2. Therefore, the aim of the present study was to modify the new in vitro model to a model that more closely resembles the in vivo model and, using the new in vitro model, to reassess the gastroprotective effects of some BZ and to assess the effects of some new compounds. 3. The rat stomach was isolated from the whole animal and kept in aerated Krebs' solution at 37 degrees C in an organ bath. Gastric mucosal damage was induced by instillation of 1 mL of 100% ethanol into the stomach. Drugs or their vehicle were administered inside the bath 15 min before ethanol instillation into the stomach. One hour after the instillation of ethanol, the stomach was removed from the organ bath, opened along the greater curvature and then examined for gastric mucosal damage. 4. The results indicate that, compared with vehicle pretreatment, ethanol-induced gastric mucosal damage was significantly reduced in a dose-dependent manner by pretreatment with clonazepam, a drug that acts as an agonist at central BZ sites of the GABAA receptor, and Ro 15-4513, a partial inverse agonist at BZ sites of the GABAA receptor. Flumazenil (an antagonist of central BZ sites of the GABAA receptor) did not affect gastric mucosal lesions provoked by ethanol. However, flumazenil significantly reversed the mucosal protective effects of clonazepam and Ro 15-4513. 5. CGS 9896 (a partial agonist at BZ sites of the GABAA receptor, with anxiolytic and anticonvulsant but no sedative effects) did not offer any protection against ethanol-induced gastric mucosal damage. Ro 5-3663, an atypical BZ that binds to the picrotoxin site of the GABAA receptor and reported to be a potent convulsant and only a weak antagonist of GABA, did not show any protection against the development of lesions. 6. The results suggest local gastric mediation of the effects of ethanol, as well as the gastric protective effects of BZ, through an action at local central-type BZ sites of the GABAA receptor located in the rat stomach.

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Effect of gamma-aminobutyric and gamma-hydroxybutyric acids on rate of14C-leucine incorporation into proteins of the gastric mucosa and hypothalamus

Cited by 2 publications

References 3 publications

Benzodiazepines protect against ethanol‐induced gastric mucosal damage in vitro*

Benzodiazepines protect against ethanol‐induced gastric mucosal damage in vitro*

Drugs acting at the GABA_A receptor attenuate ethanol‐induced gastric mucosal damage *in vitro**

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Effect of gamma-aminobutyric and gamma-hydroxybutyric acids on rate of14C-leucine incorporation into proteins of the gastric mucosa and hypothalamus

Cited by 2 publications

References 3 publications

Benzodiazepines protect against ethanol‐induced gastric mucosal damage in vitro*

Benzodiazepines protect against ethanol‐induced gastric mucosal damage in vitro*

Drugs acting at the GABAA receptor attenuate ethanol‐induced gastric mucosal damage in vitro*

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Drugs acting at the GABA_A receptor attenuate ethanol‐induced gastric mucosal damage *in vitro**