ABSTRACT
Many scientists in the fields of pharmacology, physiology, and electrophysiology are focusing their efforts towards understanding the detailed mechanisms involved in cannabinoid receptor signal transduction. With cloned receptors, specific antagonists, and powerful approaches afforded to us through the use of molecular and cellular biology, an understanding of in vivo outcomes is being revealed by in vitro events. Like many other G-protein coupled receptors, cannabinoid receptors can activate a range of signal transduction pathways. This chapter reviews the studies to date that have investigated the type of G-proteins activated by cannabinoid receptors and the regions of these proteins involved in the interactions. We next consider the result of this activation on intracellular alterations in adenylate cyclase activity, modulation of ion channels, release of calcium from intracellular stores, and activation of transcription factors. This chapter also addresses the apparent constitutively active nature of cannabinoid receptors by discussing their susceptibility to inverse agonists. Receptor activation is a dynamic response which must be regulated by feedback mechanisms in order to achieve homeostasis within a physiological system. We consider these characteristics by relating in vivo tolerance to many recent in vitro studies that have investigated receptor desensitization, internalization, and up-regulation. Taken together the studies presented will demonstrate cannabinoid receptor mediated signal transduction to be a highly complex process which requires future investigation.
