Dual effects of 5-HT4 receptor activation on GABA release from guinea pig hippocampal slices.
The effects of BIMU-8, a 5-HT4 receptor agonist, were studied on GABA release in guinea pig hippocampal slices. BIMU-8 did not modify GABA outflow at rest but did display a complex action in electrically stimulated slices: at low concentrations it increased, and at higher concentrations inhibited, GABA release. These responses were competitively counteracted by GR 125487, a selective 5-HT4 receptor antagonist. The dual effects of BIMU-8 are consistent with its indirect cholinergic action since the M1 and M3 antagonist, 4-DAMP, prevented BIMU-8-elicited GABA facilitation, whereas the M2 antagonist AFDX-116 cancelled GABA inhibition. These results provide evidence that serotonin exerts a complex modulation on the GABAergic system, via 5-HT4 receptors, and suggest that the amine releases acetylcholine which, in turn, bidirectionally modulates GABA release.
Bianchi
Clementina
C
Department of Clinical and Experimental Medicine: Section of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy. bnc@unife.it
Rodi
Donata
D
Marino
Silvia
S
Beani
Lorenzo
L
Siniscalchi
Anna
A
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C070189:(endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine