Ontogeny of Endocannabinoid Modulation of Neuromuscular Transmission: Contribution of Postsynaptic Nicotinic Receptors and Butyrylcholinesterase-Sensitive Mechanisms

Endocannabinoid receptors of the CB1 subtype are the most abundant G-protein-coupled receptors in the central nervous system, where they strongly regulate neurotransmitter release. The effects of the activation of these receptors by exogenously applied agonists have also been described in the peripheral nervous system, particularly at neuromuscular junctions (NMJs). However, the physiological role of these receptors at NMJs has not been demonstrated. We have shown that blockade of CB1 receptors at the NMJs of newborn or young mice increases the quantal content of end-plate potentials, as well as their decay time constant. Neither effect of CB1 receptor blockade is observed if postsynaptic muscle acetylcholine receptors are partially blocked. Thus, CB1 receptors may be involved in maintaining synaptic homeostasis. Importantly, the effect of CB1 receptor blockade on quantal content is potentiated by blockade of the enzyme butyrylcholinesterase. Therefore, butyrylcholinesterase may be considered a component of the extracellular degradation system for endocannabinoids.