Tumour necrosis factor alpha suppression by MDMA is mediated by peripheral heteromeric nicotinic receptors.
MDMA is an illegal drug widely used by young people. The present study aimed to determine the involvement of different nicotinic acetylcholine receptor (nAChR) subtypes in the suppressive effect of MDMA in TNF-alpha production. Dihydrobetaerythroidine (antagonist of heteromeric nAChR), and hexamethonium (antagonist of peripheral nAChR), fully antagonized the effect of MDMA. Conversely, methyllycaconitine (antagonist of homomeric nAChR), did not modify it. From in vitro experiments, a direct effect was ruled out. In this study we provide the first evidence that in rodents MDMA impairs the production of TNF-alpha by activation of heteromeric nAChR expressing beta-2 subunits located in the periphery.
Camarasa
Jorge
J
Laboratory of Pharmacology and Pharmacognosy, Institute of Biomedicine, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. jcamarasa@ub.edu
Ros
Clara
C
Pubill
David
D
Escubedo
Elena
E
D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D013287:Illicit Drugs / Q000009:adverse effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology
D013287:Illicit Drugs; D008070:Lipopolysaccharides; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4