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Anandamide induces cough in conscious guinea‐pigs through VR1 receptors
Author(s) -
Jia Yanlin,
McLeod Robbie L,
Wang Xin,
Parra Leonard E,
Egan Robert W,
Hey John A
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704950
Subject(s) - anandamide , capsazepine , cannabinoid receptor , chemistry , endocannabinoid system , cannabinoid , trpv1 , pharmacology , receptor , guinea pig , medicine , endocrinology , agonist , biology , biochemistry , transient receptor potential channel
Endogenous neuronal lipid mediator anandamide, which can be synthesized in the lung, is a ligand of both cannabinoid (CB) and vanilloid receptors (VR). The tussigenic effect of anandamide has not been studied. The current study was designed to test the direct tussigenic effect of anandamide in conscious guinea‐pigs, and its effect on VR1 receptor function in isolated primary guinea‐pig nodose ganglia neurons. Anandamide (0.3–3 mg·ml −1 ), when given by aerosol, induced cough in conscious guinea‐pigs in a concentration dependent manner. When guinea‐pigs were pretreated with capsazepine, a VR1 antagonist, the anandamide‐induced cough was significantly inhibited. Pretreatment with CB1 (SR 141716A) and CB2 (SR 144528) antagonists had no effect on anandamide‐induced cough. These results indicate that anandamide‐induced cough is mediated through the activation of VR1 receptors. Anandamide (10–100 μ M ) increased intracellular Ca 2+ concentration estimated by Fluo‐4 fluorescence change in isolated guinea‐pig nodose ganglia cells. The anandamide‐induced Ca 2+ response was inhibited by two different VR1 antagonists: capsazepine (1 μ M ) and iodo‐resiniferatoxin (I‐RTX, 0.1 μ M ), indicating that anandamide‐induced Ca 2+ response was through VR1 channel activation. In contrast, the CB1 (SR 141716A, 1 μ M ) and CB2 (SR 144528, 0.1 μ M ) receptor antagonists had no effect on Ca 2+ response to anandamide. In conclusion, these results provide evidence that anandamide activates native vanilloid receptors in isolated guinea‐pig nodose ganglia cells and induces cough through activation of VR1 receptors.British Journal of Pharmacology (2002) 137 , 831–836. doi: 10.1038/sj.bjp.0704950