Document Detail

Cellular mechanisms of serotonin 5-HT2A receptor-mediated cGMP formation: the essential role of glutamate.
MedLine Citation:
PMID:  15019576     Owner:  NLM     Status:  MEDLINE    
The current study explores the mechanisms by which activation of serotonin(2A) (5-HT(2A)) receptors increase production of cyclic guanosine monophosphate (cGMP) in slices of rat frontal cortex. Contrary to results in cortical slices, stimulation of 5-HT(2A) receptors in cells stably expressing this serotonin receptor did not alter cGMP levels. In cortical slices, stimulation of cGMP formation by 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-HT(2A/2C) receptor agonist, was blocked by tetanus toxin, a substance that prevents vesicular neurotransmitter release. However, this stimulation was not altered by tetrodotoxin, an agent that inhibits depolarization-induced neurotransmitter release. Addition of an N-methyl-d-aspartate (NMDA) receptor antagonist, d-AP-7, but not of an AMPA/kainate receptor antagonist CNQX, completely inhibited DOM-mediated cGMP production in the slices. Combined application of maximally effective concentrations of NMDA and DOM elicited a greater increase in cGMP content than either drug alone. The present study shows that 5-HT(2A) receptors do not directly stimulate cGMP formation, but rather that 5-HT(2A) receptor-mediated cGMP production is dependent on extracellular glutamate activating NMDA receptors. The results indicate that 5-HT(2A) receptor-mediated cGMP production could be at least partially attributed to potentiation of NMDA receptor-mediated cGMP formation.
Meredith J Regina; Robert C Bucelli; Jerrold C Winter; Richard A Rabin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  1003     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-15     Completed Date:  2004-07-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  168-75     Citation Subset:  IM    
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, 102 Farber Hall, State University of New York at Buffalo, Buffalo, NY 14214-3000, USA.
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MeSH Terms
Brain / cytology,  drug effects,  metabolism
Cyclic GMP / metabolism*
Glutamic Acid / physiology*
N-Methylaspartate / pharmacology
PC12 Cells
Rats, Inbred F344
Receptor, Serotonin, 5-HT2A / agonists,  metabolism*
Receptors, N-Methyl-D-Aspartate / agonists,  metabolism
Serotonin Agonists / pharmacology
Grant Support
Reg. No./Substance:
0/Receptor, Serotonin, 5-HT2A; 0/Receptors, N-Methyl-D-Aspartate; 0/Serotonin Agonists; 56-86-0/Glutamic Acid; 6384-92-5/N-Methylaspartate; 7665-99-8/Cyclic GMP

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