GABA(B)-receptor mediation of the inhibitory effect of gamma-hydroxybutyric acid on intestinal motility in mice.
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.
Carai
Mauro A M
MA
Neuroscienze S.c.a r.l., Via Palabanda 9, I-09123, Cagliari, Italy.
Agabio
Roberta
R
Lobina
Carla
C
Reali
Roberta
R
Vacca
Giovanni
G
Colombo
Giancarlo
G
Gessa
Gian Luigi
GL
D000818:Animals; D001567:Benzocycloheptenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058788:GABA-B Receptor Antagonists; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009025:Morpholines / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000378:metabolism*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D001567:Benzocycloheptenes; D058788:GABA-B Receptor Antagonists; D006885:Hydroxybutyrates; D009025:Morpholines; D018080:Receptors, GABA-B; C066471:NCS 382; C111420:4-hydroxybutyric acid