Characterization of cannabinoid receptors coupled to vasorelaxation by endothelium-derived hyperpolarizing factor
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We have recently proposed that an endogenous cannabinoid may be an endothelium-derived hyperpolarizing factor (EDHF), and we have now characterized the cannabinoid receptors mediating these responses. EDHF-mediated vasorelaxations to carbachol (ED50=3.26±0.57 nmol; the maximum relaxation, R max=87.0±2.5%) were opposed by the selective cannabinoid CB1 antagonist, LY320135: at 2 µM ED50 for carbachol was 10.4±2.6 nmol and R max was 66.9±6.2%, at 10 µM ED50 was 15.9±4.0 nmol and R max was 34.0±4.3%. However, these responses were unaffected by another putative CB1 ligand, AM630 (10 µM), or a CB2 selective antagonist, SR144528 (100 nM–1 µM). None of the antagonists influenced vasorelaxation to either the potassium channel activator levcromakalim or sodium nitroprusside. Coupled to our previous observation that the CB1 receptor antagonist SR141716A opposes EDHF-mediated relaxation, the present observations point to the involvement of a cannabinoid receptor, which may be CB1 or CB1-like, in EDHF-mediated vasorelaxation.
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