Central action of γ-aminobutyric acid ligands to alter basal water and electrolyte absorption in the rat ileum

Abstract

The γ-aminobutyric acid agonist muscimol and the γ-aminobutyric acid antagonist bicuculline were studied to determine their effects on basal net water and electrolyte transport in the rat ileum. Whereas the intraperitoneal injection of muscimol caused a reversible, dose-dependent decrease in net water absorption, bicuculline produced a reversible, dose-dependent increase in net water and ion absorption. The threshhold doses of muscimol and bicuculline were > 2.1 and 2.2 μg/kg, respectively. Lower doses of muscimol (0.1 μg) or bicuculline (0.3 μg) administered into the cerebrospinal fluid had the same effect as higher doses given systemically. Vagotomy prevented the effect of intracerebroventricular muscimol. Atropine (6 μg intracerebroventricularly) alone did not alter basal water absorption but abolished the muscimol effect, suggesting that muscimol promoted the release of acetylcholine from central cholinergic neurons. Atropine did not prevent the bicuculline effect. We conclude that (a) muscimol decreases ileal water absorption and bicuculline enhances ileal water absorption by an action at a γ-aminobutyric acid receptor in the central nervous system, (b) the muscimol effect is due to an alteration in parasympathetic vagal outflow to the intestine, (c) the muscimol effect is mediated by a central cholinergic interneuron, and (d) the bicuculline effect is not mediated by the release of acetylcholine from central cholinergic neurons.