The role of various calcium and potassium channels in the regulation of somatodendritic serotonin release.
We prepared slices from midbrain containing the raphe nuclei and from hippocampus of rats. The brain slices were loaded with [3H]serotonin and superfused in order to measure the release of radioactivity at rest and in response to electrical stimulation. No difference was observed in the resting and stimulated fractional release of tritium in the somatodendritic and axon terminal parts of serotonergic neurons. The selective 5-HT1A receptor agonist 8-OH-DPAT decreased the electrically induced tritium efflux from raphe nuclei slices preloaded with [3H]serotonin, and this inhibition was reversed by the 5-HT1A receptor antagonist (+)WAY-100135. The 5-HT1B receptor agonist CGS-12066B but not 8-OH-DPAT, inhibited the stimulation-evoked tritium efflux from hippocampal slices after labeling with [3H]serotonin. The electrical stimulation-evoked tritium efflux in raphe nuclei slices incubated with [3H]serotonin was completely external Ca(2+)-dependent, and omega-conotoxin GVIA and Cd2+, but not diltiazem, inhibited the tritium overflow. In raphe nuclei slices 4-aminopyridine enhanced the electrical stimulation-induced tritium release in a concentration-dependent manner. The inhibition of tritium efflux by 8-OH-DPAT was abolished with 4-aminopyridine. Glibenclamide or tolbutamide proved to be ineffective. These data indicate that (1) different 5-HT receptor subtypes (5-HT1A and 5-HT1B) regulate dendritic and axon terminal 5-HT release; (2) serotonin release from the dendrites may be regulated by the voltage-sensitive N-type Ca2+ channels; (3) the 5-HT1A receptor-mediated inhibition of serotonin release may be due to opening of voltage-sensitive K+ channels.
Bagdy
E
E
Institute for Drug Research, Budapest, Hungary.
Harsing
L G
LG
D000818:Animals; D001369:Axons / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014316:Tritium
D015220:Calcium Channels; D010879:Piperazines; D015221:Potassium Channels; D011810:Quinoxalines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014316:Tritium; C052561:CGS 12066B; C081293:WAY 100135; D012701:Serotonin