TI: Receptor-independent effects of natural cannabinoids
in rat peritoneal mast cells in vitro.
AU: Bueb,-J-L; Lambert,-D-M; Tschirhart,-E-J
AD: Neuroimmunology and Inflammation, Centre de Recherche Public-Sante,
Luxembourg, Belgium. jean-luc.bueb@crp-sante.lu
SO: Biochim-Biophys-Acta. 2001 Apr 23; 1538(2-3): 252-9
JN: Biochimica-et-biophysica-acta
PY: 2001
AB: Cannabinoids can activate CB(1) and CB(2) receptors. Since
a CB(2) mRNA has been described in rat peritoneal mast cells (RPMC), we
investigated a series of cannabinoids and derivatives for their capacity
to stimulate RPMC. Effects of natural cannabinoids Delta(9)-tetrahydrocannabinol
(Delta(9)-THC), Delta(8)-THC, endocannabinoids (anandamide, palmitoylethanolamide)
and related compounds (N-decanoyl-, N-lauroyl-, N-myristoyl-, N-stearoyl-
and N-oleoyl-ethanolamines; N-palmitoyl derivatives (-butylamine, -cyclohexylamine,
-isopropylamine); and N-palmitoyl, O-palmitoylethanolamine), and synthetic
cannabinoids including WIN 55,212-2, SR141716A and SR144528 were assessed
for their capacity to induce histamine release or prime RPMC stimulated
by compound 48/80. Only Delta(9)-THC and Delta(8)-THC could induce non-lytic,
energy- and concentration-dependent histamine releases from RPMC (respective
EC(50) values: 23.5+/-1.2; 53.4+/-20.6 microM, and maxima: 71.2+/-5.5;
55.7+/-2.7% of the total RPMC histamine content). These were not blocked
by CB(1) (SR141716A) or CB(2) (SR144528) antagonists, but reduced by pertussis
toxin (100 ng/ml). Endocannabinoids and analogues did neither induce histamine
secretion, nor prime secretion induced by compound 48/80 (0.2 microg/ml).
Delta(9)-THC and Delta(8)-THC induced in vitro histamine secretion from
RPMC through CB receptor-independent interactions, partly involving G(i/o)
protein activation.