5-HT7 receptors modulate synchronized network activity in rat hippocampus.
In the CA3 region of rat hippocampal slices gamma-amino-butyric acid (GABA)(A/B) receptor antagonists induce low frequency bursting activity that was either inhibited (in 21% of slices) or increased by the selective 5-HT receptor agonists 5-carboxy-tryptamine (0.1-1 microM) and 8-hydroxydipropylaminotetralin (8-OH-DPAT). The selective 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide (WAY 100635) reversed the depression of bursting activity whereas the 5-HT7 receptor antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970; 1-10 microM), but not the 5-HT1A, 4 or 6 receptor antagonists WAY100635 (10 microM), SB-204070 (10 microM) and SB-271046 (10 microM), reversed the increase in bursting activity. The apparent -log10 K(D) value (8.4) for the effect of SB-269970 was consistent with a selective action at 5-HT7 receptors. Accompanying the 5-CT-induced increase in bursting frequency there was a shortening of the burst event waveform and a reduction in the after-hyperpolarization following each bursting event both of which were inhibited by SB-269970. These effects appeared to result predominantly from a direct 5-HT(7) receptor-mediated inhibition of a Ca2+ activated K+ channel.
Gill
Catherine H
CH
Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Third Avenue, CM19 5AW, Harlow, UK.
Soffin
Ellen M
EM
Hagan
Jim J
JJ
Davies
Ceri H
CH
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D005110:Extracellular Space; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008839:Microelectrodes; D009415:Nerve Net / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D004146:Dioxanes; D010879:Piperazines; D010880:Piperidines; D024681:Potassium Channels, Calcium-Activated; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; C084858:SB 204070A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin