In vivo effects of gamma-aminobutyric acid on the urinary bladder contraction accompanying micturition.
We studied the effects of the gamma-aminobutyric acid (GABA) receptor agonists, diazepam and muscimol, on the urinary bladder contraction induced by infusion of Tyrode's solution into the bladder in anesthetized rats. Diazepam (1 mg/kg, i.p.) completely inhibited bladder contraction, causing the bladder pressure to rise until solution leaked from the penis. The inhibitory effects of diazepam were reversed by picrotoxin (1 mg/kg, i.v., twice with an interval of 10 min), and the effects were potentiated and attenuated by pretreatment with aminooxyacetic acid (AA, 10 mg/kg, i.v.) and semicarbazide (200 mg/kg, i.v.), respectively. Only pretreatment with AA inhibited the bladder contraction induced by infusion of Tyrode's solution into the bladder in six out of eight rats. Diazepam abolished efferent discharges recorded from the left pelvic nerve, but hexamethonium facilitated the generation of efferent discharges after inhibition of bladder contraction. After complete inhibition of bladder contraction by diazepam, electrical stimulation of the left pelvic nerve at 5 Hz for 30 sec was able to induce bladder contraction, and this resulted in micturition. Intracerebroventricular injection or intrathecal injection into the sacral part of the spinal cord of 1 microgram muscimol completely inhibited the bladder contraction. It was considered that the inhibitory effects of GABA receptor agonists on bladder contraction were mainly induced through the GABA receptors in the micturition center of the sacral cord, as well as the brain stem.
Kontani
H
H
Department of Pharmacology, Hokuriku University, School of Pharmacy, Kanazawa, Japan.
Kawabata
Y
Y
Koshiura
R
R
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D004558:Electric Stimulation; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009476:Neurons, Efferent / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012663:Semicarbazides / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D014554:Urination; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000625:Aminooxyacetic Acid; D003975:Diazepam; D006584:Hexamethonium Compounds; D009118:Muscimol; D010852:Picrotoxin; D012663:Semicarbazides; D005680:gamma-Aminobutyric Acid