Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide.

Abstract

Mast cells are multifunctional bone marrowderived cells found in mucosal and connective tissues and in the nervous system, where they play-important roles in tissue inflammation and in neuroimmune interactions. Very

Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide

“…Further support to this proposal comes from the fact that palmitylethanolamide may exert both analgesic Ž . Calignano et al, 1998;Jaggar et al, 1998; present study Ž and anti-inflammatory effects Benvenuti et al, 1968;Facci . et al, 1995;Mazzari et al, 1996 .…”

“…Palmitylethanolamide, which was isolated from tissues more than Ž . three decades ago Bachur et al, 1965 , was shown to have Ž marked anti-inflammatory Benvenuti et al, 1968;Facci et . al., 1995;Mazzari et al, 1996 and antinociceptive effects Ž when administered as a drug Calignano et al, 1998;.…”

Characterization of palmitoylethanolamide transport in mouse Neuro‐2a neuroblastoma and rat RBL‐2H3 basophilic leukaemia cells: comparison with anandamide

“…The mechanism appears to be mediated by a speci®c Na + -independent carrier protein in as much as it is saturable, temperature-dependent, selective, and apparently inhibited by various AEA analogues such as AM404 (for review, see Hillard & Jarrahian, 2000). The presence of a de®ned transport mechanism for PEA would provide an interesting pharmacological target for the treatment of in¯ammatory diseases, since a blockade of PEA transport would result in elevated extracellular concentrations of PEA, and hence, augmentation of the anti-in¯ammatory and anti-nociceptive e ects of this compound (Facci et al, 1995;Mazzari et al, 1996;Jaggar et al, 1998;Calignano et al, 1998). This would be analogous to the situation for AEA, where both the duration and intensity of the hypotensive e ects of i.v.…”

“…With regard to PEA, Facci et al (1995) proposed that it acts as an endogenous physiological ligand for the CB 2 receptor. However, more recent data have indicated that PEA does not bind with high a nity to either of the two cannabinoid receptor subtypes (Showalter et al, 1996;antagonizing in¯ammatory processes (Facci et al, 1995;Mazzari et al, 1996).…”

“…However, more recent data have indicated that PEA does not bind with high a nity to either of the two cannabinoid receptor subtypes (Showalter et al, 1996;antagonizing in¯ammatory processes (Facci et al, 1995;Mazzari et al, 1996). Furthermore, peripheral administration of PEA produces an analgesic e ect in formalin-induced in¯ammatory pain (Jaggar et al, 1998;Calignano et al, 1998), and the PEA-induced anti-nociceptive e ects are believed to be mediated by a peripheral CB 2 -like receptor.…”