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GABA(B)-receptor mediation of the inhibitory effect of gamma-hydroxybutyric acid on intestinal motility in mice
Authors:Carai Mauro A M  Agabio Roberta  Lobina Carla  Reali Roberta  Vacca Giovanni  Colombo Giancarlo  Gessa Gian Luigi
Institution:Neuroscienze S.c.a r.l., Via Palabanda 9, I-09123, Cagliari, Italy.
Abstract:The effect of acutely administered gamma-hydroxybutyric acid (GHB) and GHB receptor antagonist, NCS-382, on the propulsive activity in the mouse small intestine was assessed by measuring the transit of an orally administered, non absorbable marker. Both GHB (0, 25, 50, 100, 200 and 300 mg/kg; i.p.) and NCS-382 (0, 25, 50 and 75 mg/kg; i.p.) induced a dose-dependent inhibition (up to 50-60%) of the marker transit. Pretreatment with the GABA(B) receptor antagonist, SCH 50911 (100 mg/kg; i.p.), resulted in the blockade of the inhibiting effect of both GHB and NCS-382. These results suggest that the constipating effect of GHB and NCS-382 are secondary to stimulation of the GABA(B) receptor.
Keywords:γ-Hydroxybutyric acid (GHB)  GHB receptor antagonist  NCS-382  GABAB receptor  GABAB receptor antagonist  SCH 50911  Small intestine  Intestinal propulsive activity  Mouse
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