Document Detail


Melittin stimulates fatty acid release through non-phospholipase-mediated mechanisms and interacts with the dopamine transporter and other membrane-spanning proteins.
MedLine Citation:
PMID:  20969853     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phospholipase A(2) releases the fatty acid arachidonic acid from membrane phospholipids. We used the purported phospholipase A(2) stimulator, melittin, to examine the effects of endogenous arachidonic acid signaling on dopamine transporter function and trafficking. In HEK-293 cells stably transfected with the dopamine transporter, melittin reduced uptake of [((3))H]dopamine. Additionally, measurements of fatty acid content demonstrated a melittin-induced release of membrane-incorporated arachidonic acid, but inhibitors of phospholipase C, phospholipase D, and phospholipase A(2) did not prevent the release. Subsequent experiments measuring [(125)I]RTI-55 binding to the dopamine transporter demonstrated a direct interaction of melittin, or a melittin-activated endogenous compound, with the transporter to inhibit antagonist binding. This effect was not specific to the dopamine transporter, as [(3)H]spiperone binding to the recombinant dopamine D(2) receptor was also inhibited by melittin treatment. Finally, melittin stimulated an increase in internalization of the dopamine transporter, and this effect was blocked by pretreatment with cocaine. Thus, melittin acts through multiple mechanisms to regulate cellular activity, including release of membrane-incorporated fatty acids and interaction with the dopamine transporter.
Authors:
Dove J Keith; Amy J Eshleman; Aaron Janowsky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-20
Journal Detail:
Title:  European journal of pharmacology     Volume:  650     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-05-02     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  501-10     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
Affiliation:
Research Service, VA Medical Center, and Graduate Program in Neuroscience, Portland, OR 97239, USA.
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MeSH Terms
Descriptor/Qualifier:
Arachidonic Acid / metabolism*
Biological Transport
Cocaine / pharmacology
Dopamine / metabolism
Dopamine Plasma Membrane Transport Proteins / genetics,  metabolism*
Drug Interactions
Enzyme Activators / pharmacology*
HEK293 Cells
Humans
Melitten / pharmacology*
Membrane Proteins / metabolism*
Phospholipase D / metabolism
Phospholipases / metabolism*
Phospholipases A2 / antagonists & inhibitors,  metabolism
Protein Transport
Type C Phospholipases / metabolism
Grant Support
ID/Acronym/Agency:
5F31DA016499-02/DA/NIDA NIH HHS; F31 DA016499-01/DA/NIDA NIH HHS; F31 DA016499-02/DA/NIDA NIH HHS; P50 DA018165/DA/NIDA NIH HHS; P50 DA018165-04/DA/NIDA NIH HHS; P50 DA018165-05/DA/NIDA NIH HHS; Y1-DA5007/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Plasma Membrane Transport Proteins; 0/Enzyme Activators; 0/Membrane Proteins; 20449-79-0/Melitten; 50-36-2/Cocaine; 506-32-1/Arachidonic Acid; EC 3.1.-/Phospholipases; EC 3.1.1.4/Phospholipases A2; EC 3.1.4.-/Type C Phospholipases; EC 3.1.4.4/Phospholipase D
Comments/Corrections

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