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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Maggi, C. A. Luzzi, S. Zilletti, L. Spagnesi, S. Giotti, A. |
| Abstract | The effect of gamma-aminobutyric acid (GABA) administration was studied in both in vitro and in vivo preparations of the guinea-pig distal colon. In in vitro preparations GABA (10(-7) - 10(-3) M) elicited a dose-dependent relaxation; a decrease in the spontaneous contractions was sometimes observed. The effect of GABA was mimicked by (-)-baclofen, which gave a dose-response curve overlapping that of GABA, while (+)-baclofen was about one hundred times less potent. The relaxation responses induced by the above drugs were antagonized by 5-aminovaleric acid (5 X 10(-4) M), which did not affect adenosine-induced relaxation, but they were insensitive to bicuculline (10(-5) M) and picrotoxin (10(-5) M). Moreover, they were prevented by tetrodotoxin (6 X 10(-7) M). In hyoscine (10(-7) M)-pretreated preparations, GABA still evoked a small relaxation response (approx. 10% of the maximum) that was bicuculline-sensitive. Desensitization to GABA (10(-5) M) was observed. A specific cross-desensitization occurred between GABA (10(-5) M) and (-)-baclofen (10(-5) M). In in vivo preparations, GABA (10 mumol kg-1) and (-)-baclofen (5 mumol kg-1) produced a dose-related inhibition of basal tone, while (+)-baclofen (5 mumol kg-1) had much less effect (about 25%). A decrease in the spontaneous contractions was sometimes observed. The relaxant effect of GABA and (-)-baclofen persisted in guinea-pigs pretreated (1-2 min) with picrotoxin (1.6 mumol kg-1), whereas it was significantly reduced in animals injected 1 min beforehand with 5-aminovaleric acid (0.2 mmol). The maximal relaxant effect induced by GABA and (-)-baclofen did not differ from that of atropine (0.9 mumol kg-1) and after atropine administration GABA had no further inhibitory effect. Relaxation responses induced by GABA and (-)-baclofen still occurred after blockade of nicotinic receptors by hexamethonium (0.17 mmol kg-1), which itself caused an increase in the basal tone. When the tone was increased by topical application of physostigmine (40 micrograms), GABA and (-)-baclofen induced a greater relaxation than that obtained in basal conditions. It is concluded that GABA, both in vitro and in vivo administration, inhibits cholinergic tone in guinea-pig distal colon and that this effect is mediated mainly by activation of GABAB receptors. Further experiments are required to ascertain the possible physiological role of a GABA-releasing neuronal system in the colon in vivo. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 84 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1985-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Amino Acids, Neutral Colon Drug Effects Parasympathetic Nervous System Receptors, GABA-A Amino Acids Pharmacology Animals Atropine Baclofen Bicuculline Blood Pressure Physiology Guinea Pigs Hexamethonium Compounds In Vitro Techniques Picrotoxin Gamma-Aminobutyric Acid Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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