The endogenous cannabinoid agonist, anandamide stimulates sensory nerves in guinea-pig airways

1 The endogenous cannabinoid agonist, anandamide produced a modest contract ile response in guinea-pig isolated bronchus compared with the vanilloid re ceptor agonist capsaicin. The contractile response to both anandamide and c apsaicin was inhibited by the vanilloid receptor antagonist, capsazepine. F urthermore, the NK2-selective antagonist, SR48968 but not the NK1-selective antagonist, SR140333 inhibited contractile responses to anandamide. 2 The contractile response to anandamide was abolished in tissues desensiti zed by capsaicin. However, anandamide failed to cross-desensitize the contr actile response to capsaicin. 3 The contractile response to anandamide was not significantly altered in t he presence of the CBI receptor antagonist, SR141716A, nor the amidase inhi bitor, phenylmethylsulphonyl fluoride (PMSF) but was significantly increase d in the presence of the neutral endopeptidase inhibitor, thiorphan. 4 The cannabinoid agonist, CP55,940 failed to significantly attenuate the e xcitatory non-adrenergic non-cholinergic (eNANC) response in guinea-pig air ways. In contrast, the ORL1 receptor agonist, nociceptin, significantly inh ibited this response. 5 The results demonstrate that anandamide induces a modest contractile resp onse in guinea-pig isolated bronchus that is dependent upon the activation of vanilloid receptors on airway sensory nerves. However, cannabinoid recep tors do not appear to play a role in this regard, nor in regulating the rel ease of neuropeptides from airway sensory nerves under physiological condit ions.