gamma-Aminobutyric acid enhances the tone of human internal anal sphincter.
The effect of gamma-aminobutyric acid (GABA) on the human internal anal sphincter was investigated. Cumulative applications of GABA produced concentration-dependent contractions (10(-8)-10(-5) M) of the isolated human sphincter. Pretreatment with bicuculline (GABAA antagonist) turned them to relaxation. Muscimol, a GABAA agonist, induced concentration-dependent contractions (10(-8)-10(-5) M); however, baclofen (GABAB agonist, 10(-8)-10(-5) M) promoted concentration-dependent relaxation of the strips. These results suggested that both excitatory GABAA receptors and inhibitory GABAB receptors exist in the internal anal sphincter. Oral administration of sodium valproate (1600 mg/day), a GABA transaminase inhibitor, enhanced the anal canal resting pressure in 10 normal volunteers. Anal manometry showed a significant elevation in tonus without affecting amplitudes or frequencies. These results indicated that endogenous GABA, which was increased by sodium valproate, produced elevations in the anal canal resting pressure through its specific receptors in the human internal anal sphincter.
Kusunoki
M
M
Second Department of Surgery, Hyogo College of Medicine, Japan.
Shoji
Y
Y
Sakanoue
Y
Y
Yanagi
H
H
Fujita
S
S
Yamamura
T
T
Utsunomiya
J
J
D001003:Anal Canal / Q000187:drug effects* / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D006801:Humans; D009118:Muscimol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D011312:Pressure; D011963:Receptors, GABA-A / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D001418:Baclofen; D001640:Bicuculline