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 (VR1). 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 neuropeptide 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 (5×10-7 M). High concentrations of AEA (5×10-5 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.
- Calcitonin gene-related peptide
- Capsaicin-sensitive sensory nerve terminals
- Substance P
ASJC Scopus subject areas