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Serotonin 5‐HT 2 receptor activation potentiates N ‐methyl‐D‐aspartate receptor‐mediated ion currents by a protein kinase C‐dependent mechanism
Author(s) -
Blank T.,
Zwart R.,
Nijholt I.,
Spiess J.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960715)45:2<153::aid-jnr7>3.0.co;2-9
Subject(s) - protein kinase c , nmda receptor , staurosporine , long term potentiation , ketanserin , agonist , 5 ht receptor , serotonin , endocrinology , chemistry , medicine , receptor antagonist , receptor , pharmacology , biology , biochemistry , kinase , antagonist
Modulation of N ‐methyl‐ D ‐aspartate (NMDA) receptor‐mediated ion currents by serotonin was investigated with a two‐electrode voltage clamp technique in Xenopus oocytes injected with rat brain RNA. After a 1‐min application of 200 nM serotonin a transient potentiation of the NMDA receptor‐mediated ion currents was observed. The serotonin‐induced enhancement was mimicked by the protein kinase C activators 1‐oleoyl‐2‐acetyl‐sn‐glycerol (100 μM) and phorbol 12‐myristate 13‐acetate (10 nM), whereas the inactive phorbol ester 4‐α‐phorbol 12‐myristate 13‐acetate (10 nM) had no effect. From these observations it was concluded that protein kinase C was involved in the enhancement of NMDA‐induced currents. In agreement with this conclusion, it was found that the serotonin effect was inhibited by the protein kinase C inhibitors sphingosine (1 μM) or staurosporine (1 μM) added 20 min before NMDA application and by oocyte injection of protein kinase C (PKC)‐inhibitor peptide (500 ng/oocyte) 1 hr prior to recordings. The serotonin receptor involved was identified as a 5‐HT 2 receptor subtype by the finding that 200 nM of the selective 5‐HT 2 receptor agonist α‐methyl‐5‐hydroxytryptamine mimicked the potentiation of NMDA‐induced ion currents by serotonin. Furthermore, the observed potentiation was significantly reduced by coapplication of serotonin with 100 μM of the selective 5‐HT 2 receptor antagonist ketanserin. These results indicate that 5‐HT 2 receptors enhance NMDA receptor function via phosphoinositol hydrolysis and subsequent stimulation of PKC. © 1996 Wiley‐Liss, Inc.