Involvement of central GABAA receptor complex in controlling the basal gastric secretory activity in pylorus-ligated...

Effect of compounds related to gamma-aminobutyric acid (GABA) receptor complex on gastric acid secretion was studied to clarify a role of endogenous GABA in controlling the basal secretory activity in pylorus-ligated rats. When pentobarbital, a GABAA stimulant, was given to pylorus-ligated rats after recovery from ether anesthesia, the drug did not modify gastric acid secretion. In contrast, pentobarbital significantly stimulated acid secretion in rats anesthetized with urethane. The basal acid secretion was much higher in the rats without urethane anesthesia. Diazepam, an agonist of the benzodiazepine (BZP) receptor, did not change gastric acid secretion in both the animal groups. Picrotoxin, pentylenetetrazol (PTZ) and bicuculline, which block GABAergic mediation, significantly reduced gastric acid secretion in rats without urethane anesthesia. Moreover, the inhibition by picrotoxin was reversed completely by pentobarbital and moderately by diazepam, while the inhibition by PTZ was partly reversed by pentobarbital but not affected by diazepam. These findings suggest that the central GABAA receptor complex may play a significant role in controlling the basal gastric secretory activity. The direct involvement of the BZP receptor may be small, if any. The stimulatory mechanism through the mediation of GABAA receptor complex appears to be demonstrable when the basal secretory activity is lowered.