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Volume 271, Number 32, Issue of August 9, 1996 pp. 19238-19242

©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

Cannabinoid Receptors Are Coupled to Nitric Oxide Release in Invertebrate Immunocytes, Microglia, and Human Monocytes

(Received for publication, April 1, 1996)

George B. Stefano § , Yu Liu and Michael S. Goligorsky §

From the Neuroscience Research Institute, State University of New York, Old Westbury, New York 11568 and Departments of § Physiology and Medicine, State University of New York, Stony Brook, New York 11794

The present study demonstrates that stereoselective binding sites for anandamide, a naturally occurring cannabinoid substance, can be found in invertebrate immunocytes and microglia. The anandamide-binding site is monophasic and of high affinity, exhibiting a Kd of 34.3 nM with a Bmax of 441 fmol/mg protein. These sites are highly selective, as demonstrated by the inability of other types of signaling molecules to displace [3H]anandamide. Furthermore, this binding site is coupled to nitric oxide release in the invertebrate tissues examined as well as in human monocytes. Interestingly, the cannabinoid-stimulated release of nitric oxide initiates cell rounding. Thus, these cannabinoid actions resemble those of opiate alkaloids. In this regard, we demonstrate that these signaling systems use the same effector system, i.e. nitric oxide release, but separate receptors. Last, the presence of a cannabinoid receptor in selected evolutionary diverse organisms indicates that this signaling system has been conserved for more than 500 million years.

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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.

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