5-HT1A receptor-mediated inhibition of N-type calcium current in acutely isolated ventromedial hypothalamic neuronal cells.
The effects of serotonin (5-hydroxytryptamine: 5-HT) and 5-HT1A agonist on voltage-gated calcium channels (VGCCs) in acutely isolated ventromedial hypothalamic (VMH) neuronal cells were studied using whole-cell configuration of the patch-clamp technique. 5-HT at 10 microM inhibited inward calcium current reversibly in 80% of cells. This inhibition was specific to N-type current. Because pindolol blocked the effect of 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) mimicked the effect of 5-HT, the inhibitory effect of 5-HT appeared to be mediated via the 5-HT1A receptor. In the fura-2 fluorometry method, 8-OH-DPAT attenuated the [Ca2+]i increase induced by the depolarization stimulus of 50 mM K+. These results indicate that 5-HT suppresses Ca2+ entry through N-type channels in the VMH neurons via the 5-HT1A receptor and that the stimulating effect of 8-OH-DPAT on feeding behavior may be mediated by the blocking of Ca2+ entry through N-type channels.
Koike
H
H
Department of Chemical Pharmacology, Faculty of Pharmacological Sciences, University of Tokyo, Japan.
Saito
H
H
Matsuki
N
N
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D015640:Ion Channel Gating / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D020866:omega-Conotoxin GVIA
D000662:Amphetamines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D020866:omega-Conotoxin GVIA; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine