Cannabinoid receptors and cellular actions of cannabinoids

The first cannabinoid receptor was cloned a decade ago. It was called CBj. This was soon followed by the cloning of a second subtype of cannabinoid receptor that was accordingly called CB2. Both receptor subtypes belong to the family of seven transmembrane domain G-protein coupled receptors (Matsuda et at., 1990; Munro et at., 1993). The CB2 cannabinoid receptor is mainly associated with the immune system. The CBX cannabinoid receptor is the receptor expressed by neurons and therefore will be the focus of interest in this chapter. In accordance, the motor effects of cannabinoids seem to be mediated by the neural CB1 cannabinoid receptor (Rinaldi-Carmona et at., 1994; Compton et at., 1996; Souilhac et at, 1995). In general, the basal effect of activating CBX cannabinoid receptors is inhibition of neurotransmission (Howlett et at., 1986; Deadwyler et at., 1993; Mackie and Hille, 1992; Mackie et at., 1995). However, a secondary opposite effect increasing the excitability of cells has also been reported (Axelrod and Felder, 1998; Fride et at, 1995; Glass and Felder, 1997; Netzeband et at., 1999). These opposite effects of the activation of CBX receptors have been suggested to depend on the level of neuronal activity. When the cell is activated, the basal action of cannabinoids inhibiting neurotransmission will be obtained. However, when there is already inhibition, the secondary activational action of cannabinoids will be noticeable. Similar opposite effects of cannabinoid action depending on the state of the system are observed within neural circuits and at the systemic level in the control of movement (as discussed below). These complex opposite actions characterize cannabinoids as neuromodulators.

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