Inhibition by 5-HT7 receptor stimulation of GABAA receptor-activated current in cultured rat suprachiasmatic neurones.
1. Whole-cell voltage-clamp recordings were made from postnatal rat suprachiasmatic (SCN) neurones to investigate possible modulation by 5-hydroxytryptamine (5-HT) of gamma-aminobutyric acid (GABA)-activated current (IGABA). 2. 5-HT reversibly inhibited IGABA in a concentration-dependent manner (10(-10) to 10(-6) M). (+/-)-8-Hydroxy-2-N,N-dipropylaminotetralin (8-OH-DPAT, 10(-10) to 10(-5) M) and 5-carboxamidotryptamine (10(-6) M) also inhibited IGABA, whereas 1-(2,5-dimethyl-4-iodophenyl)-2-aminopropane (DOI, 10(-6) M) had no significant effect. 3. The effect of 8-OH-DPAT (10(-7) M) was blocked by ritanserin (10(-7) M), but not by pindolol (10(-7) M). The effect of 5-HT was also suppressed by ritanserin, but not by pindolol, ketanserin (10(-7) M) or ICS 205-930 (10(-6) M). 4. 8-Bromo-cAMP (10(-3) M) or forskolin (5 x 10(-5) M) suppressed IGABA. The effects of forskolin and 5-HT were not additive. Furthermore, the effect of 5-HT (10(-7) M) was significantly reduced by N-[2-(methylamino)ethyl]-5-isoquinoline sulphonamide (H-8, 10(-6) M). 5. It is concluded that 5-HT inhibits IGABA in the SCN neurones, which involves the activation of 5-HT7 receptors and cAMP-coupled systems.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
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Kawahara
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Saito
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Katsuki
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D016713:Ritanserin; D005576:Colforsin; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP