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Anandamide regulates neuropeptide release from capsaicin‐sensitive primary sensory neurons by activating both the cannabinoid 1 receptor and the vanilloid receptor 1 in vitro
Author(s) -
Ahluwalia Jatinder,
Urban Laszlo,
Bevan Stuart,
Nagy Istvan
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02703.x
Subject(s) - anandamide , cannabinoid receptor , chemistry , trpv1 , cannabinoid , calcitonin gene related peptide , capsaicin , endocannabinoid system , endocrinology , medicine , capsazepine , gpr18 , pharmacology , receptor , neuropeptide , antagonist , biology , transient receptor potential channel , biochemistry
The effect of anandamide, which activates both the cannabinoid 1 (CB1) receptor and the vanilloid receptor 1 (VR1), was studied on calcitonin gene‐related peptide (CGRP) release from cultured primary sensory neurons, the majority of which coexpress the CB1 receptor and VR1. Concentrations of anandamide < 1 µ m produced a small but significant CB1 receptor‐mediated inhibition of basal CGRP release while higher concentrations induced VR1‐mediated CGRP release. The excitatory effect of anandamide was potentiated by the CB1 receptor antagonist SR141716A. In the presence of SR141716A at concentrations < 100 n m , anandamide was equipotent with capsaicin in stimulating CGRP release. However, at higher concentrations anandamide produced more CGRP release than equimolar concentrations of capsaicin. Three and ten nanomolar anandamide inhibited the capsaicin‐evoked CGRP release. In the presence of SR141716A, treatments which activated protein kinase A, protein kinase C and phospholipase C significantly potentiated the anandamide‐evoked CGRP release at all anandamide concentrations. Although this potentiation was reduced when the CB1 receptor antagonist was omitted from the buffer, the CGRP release evoked by 300 n m and 1 µ m anandamide was still significantly larger than that seen with nonpotentiated cells. These data indicate that anandamide may regulate CGRP release from capsaicin‐sensitive primary sensory neurons in vivo , and that the net effect of anandamide on transmitter release from capsaicin‐sensitive primary sensory neurons depends on the concentration of anandamide and the state of the CB1 receptor and VR1. These findings also suggest that anandamide could be one of the molecules responsible for the development of inflammatory heat hyperalgesia.