Inhibition in the human urinary bladder by gamma-amino-butyric acid.
OBJECTIVE
To investigate the effects of gamma-amino-butyric acid (GABA) on detrusor activity in man to determine whether it has any inhibitory effect on detrusor contraction. The inhibitory neurotransmitter GABA has been found in mammalian urinary bladders and the effects of GABA on detrusor activity in the rabbit bladder has previously been described [1].


METHODS
Human detrusor muscle strips, obtained at cystectomy, were made to contract by electrical stimulation of their autonomic nerves or by the addition of carbachol in a superfusion apparatus. GABA and its analogues were added to the superfusion chamber and any changes in the responses were measured.


RESULTS
The electrically evoked nerve-mediated contractions in human bladder muscle were exclusively cholinergic. GABA inhibited nerve-mediated contractions in human detrusor muscle-strips by the activation of the GABAB receptor, since baclofen (a GABAB receptor agonist) produced similar inhibition and muscimol (a GABAA receptor agonist) did not. There was no inhibition of carbachol-mediated contractions by GABA.


CONCLUSIONS
This in vitro study shows that GABA has a peripherally mediated inhibitory effect on excitatory neurotransmission in human detrusor muscle. The site of action is on the post-ganglionic nerves and appears to be mediated via the GABAB receptor.
Chen
T F
TF
Department of Urology, Addenbrooke's Hospital, Cambridge, UK.
Doyle
P T
PT
Ferguson
D R
DR
D000368:Aged; D002217:Carbachol / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D018756:GABA Antagonists; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D002217:Carbachol