Article date: 1985/6/1
PubMed ID: 2991291
Journal name: Journal of autonomic pharmacology (ISSN: 0144-1795)
The effects of GABA and related substances were examined in isolated detrusor strips from the dome of the guinea-pig urinary bladder. GABA (0.01-1 mM) produced concentration-related phasic contractions of isolated strips from the guinea-pig urinary bladder dome. This effect of GABA was mimicked by homotaurine and muscimol, selective GABAA receptor agonists but not by (+/-)-baclofen, a selective GABAB receptor agonist. A specific cross desensitization was observed between GABA, homotaurine and muscimol but not between (+/-)-baclofen and GABA. GABA (1 mM)-induced contractions were antagonized by picrotoxin, a selective GABAA receptor antagonist. GABA-induced contractions were almost abolished by tetrodotoxin (0.5 microM, TTX) thus indicating their neurogenic origin. In addition GABA-induced contractions were partially antagonized by atropine (to about the same extent as those produced by dimethylphenylpiperazinium (DMPP), a ganglionic stimulant), but were unaffected by hexamethonium (10 microM), phentolamine (0.2 microM) or indomethacin (5 microM). In the presence of GABA the contractile effect of both DMPP (TTX-sensitive) and acetylcholine (ACh, TTX-insensitive) were significantly reduced. Similar findings were obtained with DMPP, i.e. in preparations exposed to this ganglionic stimulant both GABA- and ACh-induced contractions were depressed. Homotaurine but not (+/-)-baclofen mimicked the depressant effect of GABA on DMPP-induced contractions. The depressant effect of GABA on ACh-induced contractions of the guinea-pig urinary bladder was neurogenic in origin, i.e., was not observed in preparations exposed to TTX. These experiments indicate that GABA has a dual effect on the contractile behaviour of the guinea-pig isolated urinary bladder. Recently it has been proposed that endogenous GABA plays a neuromodulatory role in this organ. Our data suggest that in the early phase of neurogenic activation of detrusor muscle (micturition reflex) GABA might transiently enhance excitatory neurotransmission followed by a more sustained inhibition of contractility.
Author List: Maggi C A, Santicioli P, Meli A
Publication Types: Journal Article
Substances mentioned in the article: Receptors, GABA-A; Picrotoxin; Taurine; Muscimol; Tetrodotoxin; Dimethylphenylpiperazinium Iodide; gamma-Aminobutyric Acid; tramiprosate; Baclofen; Acetylcholine; Indomethacin;
Mesh terms: Acetylcholine/pharmacology; Animals; Baclofen/pharmacology; Dimethylphenylpiperazinium Iodide/pharmacology; Drug Interactions; Guinea Pigs; In Vitro Techniques; Indomethacin/pharmacology; Male; Muscimol/pharmacology; Muscle Contraction/drug effects; Muscle, Smooth/drug effects; Picrotoxin/pharmacology; Receptors, GABA-A/drug effects; Taurine/analogs & derivatives; Tetrodotoxin/pharmacology; Urinary Bladder/drug effects; gamma-Aminobutyric Acid/pharmacology;