The role of the sympathetic nervous system and uncoupling proteins in the thermogenesis induced by 3,4-methylenedioxymethamphetamine.
Body temperature regulation involves a homeostatic balance between heat production and dissipation. Sympathetic agents such as 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) can disrupt this balance and as a result produce an often life-threatening hyperthermia. The hyperthermia induced by MDMA appears to result from the activation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-thyroid/adrenal axis. Norepinephrine release mediated by MDMA creates a double-edged sword of heat generation through activation of uncoupling protein (UCP3) along with alpha1- and beta3-adrenoreceptors and loss of heat dissipation through SNS-mediated vasoconstriction. This review examines cellular mechanisms involved in MDMA-induced thermogenesis from UCP activation to vasoconstriction and how these mechanisms are related to other thermogenic conditions and potential treatment modalities.
Mills
Edward M
EM
The National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892-1770, USA.
Rusyniak
Daniel E
DE
Sprague
Jon E
JE
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D006213:Hallucinogens; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; D018817:N-Methyl-3,4-methylenedioxyamphetamine