CANNABINOID RECEPTORS ARE COUPLED TO NITRIC-OXIDE RELEASE IN INVERTEBRATE IMMUNOCYTES, MICROGLIA, AND HUMAN MONOCYTES

The present study demonstrates that stereoselective binding sites for anandamide, a naturally occurring cannabinoid substance, can be found ill invertebrate immunocytes and microglia. The anandamide-binding sit e is monophasic and of high affinity, exhibiting a K-d of 34.3 nw with a B-max of 441 fmol/mg protein. These sites are highly selective, as demonstrated by the inability of other types of signaling molecules to displace [H-3]anandamide, Furthermore, this binding site is coupled t o 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 act ions resemble those of opiate alkaloids, In this regard, we demonstrat e that these signaling systems use the same effector system, i.e, nitr ic oxide release, but separate receptors, Last., the presence of a can nabinoid receptor in selected evolutionary diverse organisms indicates that this signaling system has been conserved for more than 500 milli on years.