ABSTRACT: The expression of genes encoding the cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase (FAAH) and the lipolytic activity of cannabinoid agonists were investigated in rat adipose tissue.RT-PCR studies indicated that the genes encoding CB1 and CB2 receptors and FAAH are not expressed in epididymal adipocytes. In functional studies, the non-selective cannabinoid receptor agonist WIN 55,212-2 concentration-dependently (0.01–30M) induced glycerol release above baseline (E
max 96.16.2% of isoprenaline-induced lipolytic response). The selective CB2 agonist JWH-015 (0.01–30M) had no lipolytic activity while the endocannabinoid 2-arachidonoylglycerol and the stable anandamide derivative, R(+)-methanandamide had, only a weak lipolytic effect at the highest concentrations employed (10 and 30M). The concentration/response relationship for WIN 55,212-2-mediated lipolytic activity, mimicked by the S(–)-enantiomer WIN 55,212-3, was shifted significantly to the right by the CB1 antagonist AM 251 only at 10M, but was not modified by the -adrenoceptor antagonist propranolol (1M). The protein kinase inhibitor H-89, but not the two adenylyl cyclase inhibitors ()N
6-R-phenylisopropyladenosine (R-PIA, 1M, a selective A1 adenosine receptor agonist) or SQ 22,536 (50M) significantly reduced the glycerol efflux induced by WIN 55,212-2.Our data suggest that the cannabinoid drug WIN 55,212-2 may exert lipolytic activity in male rat adipocytes via an intracellular mechanism, not activated by CB1 or CB2 receptor stimulation, significantly reversed by H-89 but not clearly linked to stimulation of adenylyl cyclase.
Archiv für Experimentelle Pathologie und Pharmakologie 10/2003; 368(5):352-359. · 2.65 Impact Factor