Modulatory activity of GABAB receptors on cholinergic tone in guinea‐pig distal colon
Open Access
- 1 April 1985
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 84 (4), 883-895
- https://doi.org/10.1111/j.1476-5381.1985.tb17383.x
Abstract
1 The effect of γ-aminobutyric acid (GABA) administration was studied in both in vitro and in vivo preparations of the guinea-pig distal colon. 2 In in vitro preparations GABA (10−7 − 10−3m) elicited a dose-dependent relaxation; a decrease in the spontaneous contractions was sometimes observed. 3 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. 4 The relaxation responses induced by the above drugs were antagonized by 5-aminovaleric acid (5 × 10−4m), which did not affect adenosine-induced relaxation, but they were insensitive to bicuculline (10−5m) and picrotoxin (10−5m). Moreover, they were prevented by tetrodotoxin (6 × 10−7m). In hyoscine (10−7m)-pretreated preparations, GABA still evoked a small relaxation response (approx. 10% of the maximum) that was bicuculline-sensitive. 5 Desensitization to GABA (10−5m) was observed. A specific cross-desensitization occurred between GABA (10−5m) and (—)-baclofen (10−5m). 6 In in vivo preparations, GABA (10 μmol kg−1) and (—)-baclofen (5 μmol kg−1) produced a dose-related inhibition of basal tone, while (+)-baclofen (5 μmol kg−1) had much less effect (about 25%). A decrease in the spontaneous contractions was sometimes observed. 7 The relaxant effect of GABA and (—)-baclofen persisted in guinea-pigs pretreated (1–2 min) with picrotoxin (1.6 μmol kg−1), whereas it was significantly reduced in animals injected 1 min beforehand with 5-aminovaleric acid (0.2 mmol). 8 The maximal relaxant effect induced by GABA and (—)-baclofen did not differ from that of atropine (0.9 μmol kg−1) and after atropine administration GABA had no further inhibitory effect. 9 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. 10 When the tone was increased by topical application of physostigmine (40 μg), GABA and (—)-baclofen induced a greater relaxation than that obtained in basal conditions. 11 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.This publication has 23 references indexed in Scilit:
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