Stimulation of N18TG2 cells by cannabinoid agonists CP55940 and WIN55212-2 increased cyclic GMP levels in an ODQ-sensitive manner. GC-beta(1) in membrane fractions was increased after 5 or 20 min stimulation, and was significantly depleted in the cytosol

by 1 h. The cytosolic pool of GC-beta(1) was replenished after 48 h of continued cannabinoid drug treatment. Translocation of GC-P, from the cytosol was blocked by the CB1 antagonist rimonabant (SR141716) and by the Gi/o inactivator pertussis toxin, indicating that the CB1 receptor and Gi/o proteins Selleck Gemcitabine are required for translocation. Long-term treatment with rimonabant or pertussis toxin reduced the amount of GC-beta(1) in the cytosolic pool. We conclude that CB1 receptors stimulate cyclic GMP production and that intracellular translocation of GC from cytosol to the membranes is intrinsic to the mechanism

and may be a tonically active or endocannabinoid-regulated process. (c) 2007 Elsevier Ltd. All rights reserved.”
“Background: Therapeutic use of unfractionated heparin and low molecular weight heparins (LMWHs) is limited by hemorrhagic adverse effects. We compared the antithrombotic effect of LMW fucoidan (LMWF) and LMWH in an experimental model. Methods: Thrombosis was induced in femoral arteries of male New Zealand White rabbits by in situ induction of endothelial AZD6094 apoptosis with staurosporine (10(-5) M for 30 min). Starting the day before apoptosis induction, the animals received subcutaneous LMWF (15 mg/kg), LMWH (enoxaparin 2.5 mg/kg) or saline solution (control group) twice a day for 4 days. Results: The degrees of apoptosis and endothelial denudation were similar in the 3 groups. The thrombotic score was significantly lower in the LMWF group than in the LMWH and control groups (p = 0.01). Tissue selleck screening library factor expression was significantly lower

in the LMWF group than in the control and LMWH groups (p = 0.01). The plasma concentration of tissue factor pathway inhibitor was significantly increased after LMWF injection (137 +/- 28 vs. 102 +/- 17; p = 0.01), whereas no change was observed after LMWH treatment. LMWF did not prolong the bleeding time or decrease platelet aggregation. Conclusions: LMWF appeared to be more effective than LMWH for preventing arterial thrombosis in this experimental model. LMWF also had a lower hemorrhagic risk than LMWH. Copyright (C) 2008 S. Karger AG, Basel.”
“CB1 receptor agonists increase the state of phosphorylation of the dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at the cAMP-dependent protein kinase site, Thr34. This effect, which occurs in the medium spiny neurons of the striatum, has been proposed to mediate the motor depressant action of cannabinoids.