Modulatory Roles of ATP and Adenosine in Cholinergic Neuromuscular Transmission

Abstract

A review of the data on the modulatory action of adenosine 5’-triphosphate (ATP), the main co-transmitter with acetylcholine, and adenosine, the final ATP metabolite in the synaptic cleft, on neuromuscular transmission is presented. The effects of these endogenous modulators on pre- and post-synaptic processes are discussed. The contribution of purines to the processes of quantal and non-quantal secretion of acetylcholine into the synaptic cleft, as well as the influence of the postsynaptic effects of ATP and adenosine on the functioning of cholinergic receptors, are evaluated. As usual, the P2-receptor-mediated influence is minimal under physiological conditions, but it becomes very important in some pathophysiological situations such as hypothermia, stress, or ischemia. There are some data demonstrating the same in neuromuscular transmission. It is suggested that the role of endogenous purines is primarily to provide a safety factor for the efficiency of cholinergic neuromuscular transmission.

Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production

“…TNAP regulates purinergic transmission in the central nervous system, and plays an important role in neuronal development, differentiation, and synaptic function [ 41 ]. TNAP inhibition also increases extracellular ATP in neurons, which can reduce motoneuron neurite extension [ 42 ], and dysregulate synaptic transmission in neuromuscular junction [ 43 ]. In addition, TNAP deficiency leads to reduced brain white matter, accompanied by decreased axonal myelination in the spinal cord and cortex [ 44 ].…”

The Endothelial Barrier Restricts Endocrine Actions to the Luminal Vascular Receptors: Changing the Paradigm: A Didactic Approach

“…Alternatively, if Ang II is interstitially present, it does not affect acetylcholine releasing nerve terminal. However, ATP is likely the endothelial paracrine mediator [13], inhibiting cholinergic nerve endings [72].…”

“…Through selective autocrine and paracrine signaling, these compartments alter each other diverse functions; "the response." The integration of this biophysical compartmentalization is far from a clear understanding [59], [60], [62], [63], [64], [71], [72].…”

Effect of endogenous purines on electrically evoked ACh release at the mouse neuromuscular junction

“…It is known that, at motor nerve terminals, ATP/adenosine diphosphate (ADP) as well as adenosine regulates neurotransmitter release when activating presynaptic inhibitory and facilitatory P2 and P1 Rs, respectively (Correia‐de‐Sá et al, 1996; De Lorenzo et al, 2004, 2006; Giniatullin & Sokolova, 1998; Salgado et al, 2000; Sebastião & Ribeiro, 2000; Sokolova et al, 2003; reviewed by Ziganshin et al, 2020). At the mouse NMJs, we have previously found that the cholinergic release is modulated by activation of inhibitory P2Y 13 Rs (De Lorenzo et al, 2006; Guarracino et al, 2016; Veggetti et al, 2008), A 1 Rs and A 3 Rs (Cinalli et al, 2013; De Lorenzo et al, 2004), and excitatory A 2A Rs (Palma et al, 2011).…”