Inhibitory role of gamma-amino-butyric acid in the rabbit urinary bladder.
Gamma-amino-butyric acid (GABA) is an established inhibitory neurotransmitter in the central nervous system (CNS) and it has also been identified in the bladder. We have investigated in the rabbit the effect of GABA on detrusor activity. Rabbit detrusor muscle strips were made to contract by electrical stimulation of their autonomic nerves or by the addition of carbachol. The addition of GABA caused substantial inhibition of muscle contraction. GABA acts on 2 classes of receptors-GABAA and GABAB. The inhibition was mediated via the GABAB receptors as its effect was mimicked by baclofen (a GABAB agonist) and inhibited by 2-hydroxysaclofen (a GABAB receptor antagonist). Inhibition was not prevented by bicuculline (a GABAA receptor antagonist). This inhibition may be due to a direct muscle effect since the inhibition, which occurred with carbachol-induced contraction, was not abolished by the addition of tetrodotoxin. GABA, acting via the GABAB receptor, produces substantial inhibition of muscle contraction in the rabbit urinary bladder. This raises the possibility of using GABAB analogues in the treatment of detrusor instability.
Chen
T F
TF
Department of Urology, Addenbrooke's Hospital, Cambridge.
Doyle
P T
PT
Ferguson
D R
DR
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D011817:Rabbits; D011963:Receptors, GABA-A / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D002217:Carbachol; D001418:Baclofen; C057491:2-hydroxysaclofen; D001640:Bicuculline