Biochem. J. (2005) 388
(465–473) (Printed in Great Britain)
Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells
Andrea L. SMALL-HOWARD*, Lori M. N. SHIMODA*, Chaker N. ADRA† and Helen TURNER*‡1
*Laboratory of Cell Biology and Immunology, Center for Biomedical Research at the Queen's Medical Center, Honolulu, HI 96813, U.S.A., †Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, U.S.A., and ‡Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, U.S.A.
Cannabinoids are broadly immunosuppressive, and anti-inflammatory properties have been reported for certain marijuana constituents and endogenously produced cannabinoids. The CB2 cannabinoid receptor is an established constituent of immune system cells, and we have recently established that the CB1 cannabinoid receptor is expressed in mast cells. In the present study, we sought to define a role for CB1 in mast cells and to identify the signalling pathways that may mediate the suppressive effects of CB1 ligation on mast cell activation. Our results show that CB1 and CB2 mediate diametrically opposed effects on cAMP levels in mast cells. The observed long-term stimulation of cAMP levels by the Gai/o-coupled CB1 is paradoxical, and our results indicate that it may be attributed to CB1-mediated transcriptional regulation of specific adenylate cyclase isoenzymes that exhibit superactivatable kinetics. Taken together, these results reveal the complexity in signalling of natively co-expressed cannabinoid receptors and suggest that some anti-inflammatory effects of CB1 ligands may be attributable to sustained cAMP elevation that, in turn, causes suppression of mast cell degranulation.
Key words: anti-inflammatory potential, cAMP, cannabinoids, immunosuppressive, mast cell, methanandamide.
Abbreviations used: AC, adenylate cyclase; AD, average difference; BMMC, bone marrow-derived mast cell; CNS, central nervous system; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; FSK, forskolin; GPCR, G-protein-coupled receptor; IBMX, isobutylmethylxanthine; MA, methanandamide; poly(A)+ RNA, polyadenylated RNA; PDE, phosphodiesterase; PTX, pertussis toxin; RT–PCR, reverse transcriptase PCR.
1To whom correspondence should be addressed, at Queen's Center for Biomedical Research, 1301 Punchbowl Street, University Tower 811, Honolulu, HI 96813, U.S.A. (email hturner@queens.org).
Received 4 October 2004/4 January 2005; accepted 25 January 2005
Published as BJ Immediate Publication 25 January 2005, DOI 10.1042/BJ20041682
The Biochemical Society, London ©2005
Editorial Advisory Panel
RSS feeds
Table of contents by email
My BJ toolbox
