Effects of gamma-aminobutyric acid and peripheral benzodiazepine ligands on duodenal bicarbonate secretion.
BACKGROUND
The effects of gamma-aminobutyric (GABA(A))-receptor ligands and peripheral-type benzodiazepine (BZ) ligands on duodenal mucosal bicarbonate secretion (DBS) were studied in thiobarbiturate-anesthetized rats.


METHODS
A segment of proximal duodenum was perfused, and bicarbonate secretion was continuously titrated by pH-stat. In some experiments the vagus nerves were dissected free and cut at the neck level.


RESULTS
Luminal GABA (10(-8) to 10(-6) M) increased (P < 0.01) DBS dose-dependently, and the GABA(A) antagonist (+)-bicuculline (0.1-2.5 mg/kg intravenously) caused a similar increase (P < 0.01) in DBS. Vagotomy abolished the latter response, suggesting a centrally elicited nervous action of bicuculline mediated by the vagal nerves. This was supported by the absence of an effect of bicuculline administered intra-arterially close to the duodenum. The GABA(A) agonist muscimol had no effect on DBS when administered intravenously (0.01-0.25 mg/kg) or into a lateral brain ventricle (2 microg/kg/h) but counteracted any stimulation by subsequent intravenous bicuculline. The 'peripheral-type' BZ agonist 4'-chlorodiazepam increased DBS when infused close intra-arterially but had no effect when administered intravenously.


CONCLUSIONS
Inhibition of GABA(A) receptors related to cholinergic excitatory pathways in the central nervous system stimulates duodenal mucosal bicarbonate secretion and may increase the local mucosal defense. The stimulation by luminal GABA may reflect modulation of the local mucosal control of duodenal bicarbonate secretion.
Säfsten
B
B
Dept. of Physiology, Uppsala University, and Uppsala University Hospital, Sweden.
Flemström
G
G
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D001640:Bicuculline / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004386:Duodenum; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001639:Bicarbonates; D018755:GABA Agonists; D018756:GABA Antagonists; D018757:GABA Modulators; D007546:Isoquinolines; D008024:Ligands; D001569:Benzodiazepines; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D001640:Bicuculline; C037850:PK 11195