The Phospholipid Environment of Activated Synaptic Membrane Receptors May Provide Both Intracellularly and Retrogradely Acting Signals for the Regulation of Neuro(Muscular) Transmission

Summary

The activation of two receptors of skeletal muscle and myotube in culture, the nicotinic acetylcholine receptor (nAChR) and the ATP-activated P₂-purinergic receptor (P₂R) resulted, in both cases, in increased intracellular levels of diacylglycerol (DAG). In the case of the receptor-ion channel macromolecule the intracellular DAG increases were seen after activation of nAChR by a cholinergic ligand and blocked by the nAChR inhibitors α-bungarotoxin or d-tubocurarine; they were dependent on the presence of external Ca²⁺, which points to the action of a phospholipase A₂, present in the membrane and activated directly, probably via a G-protein, by nAChR. In the second case the P₂R activates a G-protein-phospholipase C system which results in phosphoinositide turnover and a simultaneous increase in inositol phosphates and DAG, followed by intracellular Ca²⁺ movement and influx of Ca²⁺. It is discussed if DAG increases, when occurring close to the sarcolemma, might result in lipoxygenase products moving into the synapse and acting as “retrograde” signals. A preliminary experiment with arachidonic acid and a mouse phrenic nerve-diaphragm preparation was performed and showed no changes in MEPPs, while higher AA concentrations may have decreased the EPPs’ amplitudes.