Concentration-dependent dual effect of anandamide on sensory neuropeptide release from isolated rat tracheae

Most actions of anandamide (AEA) are mediated by the cannabinoid 1 (CB1) receptor activation, but on sensory neurones it is also an agonist on the vanilloid subtype 1 receptor CR1). The aim of the present study was to analyse the effect of AEA (10(-6)-10(-4) M) on inhibitory CB1 and excitatory VR1 receptors by measuring sensory neuropepticle release such as somatostatin, substance P and calcitonin gene-related peptide, from isolated rat tracheae. AEA (10(-6) M) vas without significant effect, 10(-5) M inhibited neuropeptide release, which was abolished by the G protein-coupled receptor blocker pertussis toxin (100 ng/ml) and the CB1 receptor antagonist SR141716A (5 x 10(-7) M). High concentrations of AEA (5 x 10(-5) M, 10(-4) M) increased the release of the peptides and this inhibition was prevented by the competitive VR1 antagonist capsazepine (10(-5) M). These results indicate a dual, concentration-dependent action of AEA on CB1 receptors and VR1 on peripheral sensory nerve terminals. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.