Are endocannabinoids involved in muscarinic acetylcholine receptor-mediated plasticity of the skeletal neuromuscular junction?

Abstract

The Cannabis sativa, or marijuana, plant has long been used by humans as a means of altering mental state. Recently, there has been a growing interest in therapeutic applications of cannabinoids, the chemical compounds that are derived from marijuana. The discovery of endocannabinoids, which are synthesized naturally in the body, and receptors for these chemicals has generated a great deal of interest in their roles in neurotransmission. Much has been learned about cannabinoid signaling in the central nervous system (CNS); however, within the context of the peripheral nervous system (PNS), relatively little is known about endocannabinoid activity. Muscarinic acetylcholine receptors (mAChRs), which, in addition to being widely found in the CNS, are present in the PNS, may have important interactions with endocannabinoids. In this review, we are interested in the possibility of interactions between mAChRs and endocannabinoids at the vertebrate neuromuscular junction. We will begin by providing an overview of cannabinoid research and drawing connections between cannabinoids and mAChRs. We will then discuss the current understanding regarding mAChR presence at the vertebrate muscular junction. We will also examine what is known about cannabinoid signaling and mAChRs in the CNS and correlate this information with the physiological effects of cannabinoids. We propose that knowledge about endocannabinoid function in the CNS can perhaps reveal information about possible roles for cannabinoids in the PNS, particularly at the vertebrate neuromuscular junction.