Abstract
Sigma receptors are intracellular receptors that interact with a variety of psychotropic ligands, including cocaine. Administration of cocaine to mice promoted the in vivo growth of a syngeneic lung cancer cell line and identical effects were observed with PRE 084, a selective sigma(1) receptor agonist. Increased tumor growth was accompanied by an increase in IL-10 and a decrease in IFN-gamma production in splenocytes and at the tumor site. The tumor-promoting effects produced by both cocaine and PRE 084 were abrogated by administration of specific antibodies to IL-10, or by administration of a sigma(1) receptor antagonist. We conclude that sigma(1) receptor ligands, including cocaine, augment tumor growth via a cytokine-dependent, receptor-mediated mechanism that involves regulation of T helper 1/T helper 2 cytokine balance.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma, Bronchiolo-Alveolar
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Anesthetics, Local / pharmacology*
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Animals
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Antibodies / pharmacology
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Cell Line, Tumor
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Cell Size / drug effects
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Cocaine / pharmacology*
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Cytokines / metabolism*
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Drug Interactions
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Ethylenediamines / pharmacology
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Interferon-gamma / metabolism
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Interleukin-10 / immunology
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Interleukin-10 / metabolism
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Mice
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Mice, Inbred BALB C
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Morpholines / pharmacology
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Neoplasms / metabolism*
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Receptors, sigma / antagonists & inhibitors
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Receptors, sigma / immunology*
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Receptors, sigma / metabolism
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Th2 Cells / drug effects
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Th2 Cells / metabolism
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Transplants
Substances
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Anesthetics, Local
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Antibodies
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Cytokines
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Ethylenediamines
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Morpholines
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Receptors, sigma
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Interleukin-10
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2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
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N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin
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Interferon-gamma
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Cocaine