ABSTRACT
Because psychotropic cannabinoids have high lipid solubility and low water solubility they were long thought to owe their pharmacological properties to an ability to perturb the phospholipid constituents of biological membranes.36 Although this mode of action cannot be excluded altogether. it is now clear that for many of the effects of cannabinoids the predominant underlying mechani sm is far more specific. More particularly, it is now known that cannabinoids act through receptors: CB, receptors (cloned in 1990), and CB2 receptors (cloned in 1993).34 Both of these receptor types are coupled through Guo proteins, negatively to adenylate cyclase and positively to mitogen-activated protein kinase. In addition, CB, receptors are coupled to ion channels through G "0 protein s, negatively to N-type and P/Qtype calcium channels and positively to A-type and inwardly rectifying potassium channels. CB I receptors may also mobilize arachidonic acid and close 5-HT 3 receptor ion channels34 and, under certain conditions, activate adenyl ate cyclase through G, proteins.4,l7 Another more recent finding is that some CB, receptors are negatively coupled to M-type potassium channels4 ' Evidence exists from cat experiments that CB, receptors are negatively coupled to voltage-gated dihydropyridine-sensitive L-type calcium channels on cerebral arterial smooth muscle cells, I'
system, this does not imply that peripheral CB , receptors are unimportant, Thus, some peripheral tissues may contain high concentrations of CB, receptors, localized in discrete regions such as nerve terminals that fonn only a small part of the total tissue mass.
