Document Detail

Tonic desensitization of hippocampal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors regulates 5-hydroxytryptamine release in vivo.
MedLine Citation:
PMID:  7535399     Owner:  NLM     Status:  MEDLINE    
Strong evidence implicates glutamate as an excitatory neurotransmitter in the central nervous system. In the present study we have investigated the effects of different concentrations of the excitatory amino acid agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid on release of 5-hydroxytryptamine in rat hippocampus using in vivo microdialysis. Infusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid at 1 microM led to an increase in dialysate 5-hydroxytryptamine. In contrast 100 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid decreased extracellular 5-hydroxytryptamine, collected in 30 min samples, and this decrease was sustained for several hours. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization is well documented in vitro, and is reversed by the drug diazoxide. We therefore studied the possibility that this was occurring in hippocampus in vivo. Collection of dialysates at 5 min time intervals revealed a brief increase in dialysate 5-hydroxytryptamine in response to 100 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, although basal level of 5-hydroxytryptamine was below the level of detection. When 100 microM agonist was co-infused with 500 microM diazoxide, a substantial and prolonged increase in dialysate 5-hydroxytryptamine was seen. Diazoxide alone was observed to cause an increase in extracellular 5-hydroxytryptamine. Diazoxide is known to active ATP-dependent K+ channels, however, cromakalim (100 microM), an activator of ATP-dependent K+ channels, reduced hippocampal 5-hydroxytryptamine release, suggesting that the effect of diazoxide is not the result of such an action.(ABSTRACT TRUNCATED AT 250 WORDS)
P S Whitton; S Maione; C S Biggs; L J Fowler
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroscience     Volume:  63     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-05-01     Completed Date:  1995-05-01     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  945-8     Citation Subset:  IM    
Department of Pharmacology, School of Pharmacy, London, U.K.
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MeSH Terms
6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
Diazoxide / pharmacology
Extracellular Space / drug effects,  metabolism
Hippocampus / drug effects,  metabolism*
Rats, Wistar
Receptors, AMPA / antagonists & inhibitors*
Serotonin / metabolism*
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Reg. No./Substance:
0/Receptors, AMPA; 115066-14-3/6-Cyano-7-nitroquinoxaline-2,3-dione; 364-98-7/Diazoxide; 50-67-9/Serotonin; 77521-29-0/alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

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