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• W2001596804 abstract "Noladin ether has recently been reported to be an endocannabinoid, with selectivity for the cannabinoid (CB) CB 1 receptor. In the present study, we investigated the effects of noladin ether in the rat isolated mesenteric arterial bed, cultured dorsal root ganglia (DRG) cells and human vanilloid (TRPV1)‐receptor‐expressing HEK293 cells (TRPV1‐HEK293 cells). Electrical field stimulation of the mesenteric bed evoked frequency‐dependent vasorelaxation due to the action of calcitonin gene‐related peptide (CGRP) released from sensory nerves. Noladin ether (0.1–3 μ M ) attenuated sensory neurogenic relaxation in a concentration‐dependent manner. Noladin ether (1 μ M ) reduced vasorelaxation at a submaximal frequency (8 Hz), from 57.3±6.8 to 23.3±3.8% ( P <0.05, n =4). The inhibitory effects of noladin ether were unaffected by the CB 1 antagonists SR141716A and LY320135, and the CB 2 antagonist SR144528 (1 μ M ). Noladin ether had no effect on vasorelaxation elicited by exogenous CGRP or capsaicin. These data suggest that noladin ether is acting at a prejunctional site and no interaction with TRPV1 is involved. In mesenteric beds from pertussis toxin (PTX)‐pretreated rats, the inhibitory actions of noladin ether on sensory neurotransmission were abolished, indicating the involvement of G i/o protein‐coupled receptors. Noladin ether evoked a concentration‐dependent increase in intracellular Ca 2+ concentration in TRPV1‐HEK293 cells at 10 μ M (36.5±3.2% of maximal capsaicin‐induced response), but it was a less potent agonist than both capsaicin and anandamide and at 1 μ M it was essentially inactive. Noladin ether (1 μ M ) had no effect on capsaicin‐evoked Ca 2+ responses in DRG cells, and produced no response alone, indicating it neither modulates nor acts directly on TRPV1 receptors. These data demonstrate that noladin ether attenuates sensory neurotransmission in rat mesenteric arteries via a non‐CB 1 non‐CB 2 PTX‐sensitive prejunctional site, independently of TRPV1 receptors. British Journal of Pharmacology (2004) 142 , 509–518. doi: 10.1038/sj.bjp.0705789" @default.
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• W2001596804 date "2004-06-01" @default.
• W2001596804 modified "2023-10-14" @default.
• W2001596804 title "Noladin ether, a putative endocannabinoid, attenuates sensory neurotransmission in the rat isolated mesenteric arterial bed <i>via</i> a non-CB₁ /CB₂ G_i/o linked receptor" @default.
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• W2001596804 doi "https://doi.org/10.1038/sj.bjp.0705789" @default.
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