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5‐Hydroxytryptamine‐mediated effects of nicotine on endogenous GABA efflux from guinea‐pig cortical slices
Author(s) -
Bianchi Clementina,
Ferraro Luca,
Tanganelli Sergio,
Morari Michele,
Spalluto Gianpiero,
Simonato Michele,
Beani Lorenzo
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb17233.x
Subject(s) - methysergide , mecamylamine , nicotine , tetrodotoxin , endocrinology , medicine , chemistry , alkaloid , guinea pig , bicuculline , pharmacology , biology , antagonist , receptor , biochemistry , stereochemistry
1 The effect of nicotine on endogenous basal GABA outflow was studied in guinea‐pig cerebral cortex slices. 2 Nicotine 1.86‐18.6 μmol 1 −1 significantly decreased the basal, tetrodotoxin‐sensitive GABA efflux, whereas at higher concentrations (186–620 μmol 1 −1 ) nicotine increased it. The inhibition was prevented by mecamylamine while the facilitation was blocked by mecamylamine, (+)‐tubocurarine and tetrodotoxin. 3 The effect of nicotine was due to an indirect 5‐hydroxytryptaminergic action. In fact, MDL 72222 (1 μmol 1 −1 ) completely prevented the alkaloid inhibition and methysergide (1 μmol 1 1 ) reversed the facilitation into inhibition; concomitant treatment with methysergide and MDL 72222 antagonized the effect of nicotine at 186 μmol 1 −14 Lower concentrations of 5‐HT (3–10 μmol 1 −1 ) decreased, whereas higher concentrations (30–100 μmol 1 −1 ) increased, spontaneous GABA outflow. The inhibition of GABA efflux was prevented by MDL 72222 whereas the facilitation was reversed by methysergide (1 μmol 1 −1 ) into inhibition, and prevented by MDL 72222 1 μmol 1 −11 . 5 These results suggest that, by activating nicotinic receptors present on 5‐hydroxytryptaminergic terminals, nicotine releases 5‐HT which, in turn, inhibits or increases the secretory activity of cortical GABA interneurones via 5‐HT 3 and methysergide‐sensitive receptors, respectively.