Metabolic stimulation of mouse spleen lymphocytes by low doses of delta9-tetrahydrocannabinol.
The present work was undertaken to study the metabolic response of mouse spleen lymphocytes to physiologically relevant doses of delta9-tetrahydrocannabinol (THC), the major active component of marijuana. At those concentrations (i.e. nanomolar range), THC induced a 2-2.5-fold stimulation of both glucose oxidation to CO2 and phospholipid synthesis from glucose. This stimulation was (i) dose-dependent up to 1 microM THC, (ii) mimicked by the synthetic cannabinoid HU-210, (iii) prevented by forskolin and pertussis toxin, and (iv) unaffected by the CB1 receptor antagonist SR141716A. THC was also able to antagonize the forskolin-induced elevation of intracellular cAMP concentration. In contrast, at non-physiological, cytotoxic doses (i.e. micromolar range) THC markedly depressed glucose metabolism in lymphocytes by a cannabinoid receptor-independent pathway. Results thus indicate that physiologically relevant doses of THC induce a metabolic stimulation of lymphocytes that seems to be mediated by a cannabinoid receptor-dependent pathway.
Sánchez
C
C
Department of Biochemistry and Molecular Biology I, Faculty of Biology, Complutense University, Madrid, Spain.
Velasco
G
G
Guzmán
M
M
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D037342:Pertussis Toxin; D010743:Phospholipids / Q000096:biosynthesis*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D013154:Spleen / Q000166:cytology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010743:Phospholipids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D013759:Dronabinol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D005947:Glucose; C062018:HU 211; D000077285:Rimonabant