Acetylcholine release at motor endplates and autonomic neuroeffector junctions: a comparison.
Acetylcholine released at motor endplates and at autonomic neuroeffector junctions binds to nicotinic and muscarinic receptors to affect the activity of the corresponding target cells. Additionally, nicotonic and muscarinic receptors modulate various intracellular regulatory pathways (second messengers, gene expression) and mediate trophic effects. To maintain homeostasis of the individual cell and of the whole organism the release of acetylcholine has to be strictly controlled within both nervous systems. The basic events of synthesis, storage, and release are comparable at motoneurones and autonomic neurones, but mechanisms regulating transmitter release appear to differ. The motor endplate can be regarded as a highly specialized synapse ensuring a focal innervation of skeletal muscle fibres. P-type calcium channels are critically involved in mediating exocytotic transmitter release. Facilitatory presynaptic receptors (nicotinic, muscarinic, alpha 1- and beta 1-adrenoceptors, calcitonin-gene-related peptide receptors, adenosine A2a receptors) mediate an increase in evoked acetylcholine release to allow rapid and maximal activation of skeletal muscles. In contrast, neuroeffector junctions innervate the effector cells in a rather scattered manner. N-type calcium channels are critically involved in exocytotic transmitter release. Inhibitory neuronal receptors (muscarinic, alpha 2- and beta-adrenoceptors, prostanoid (airways), receptors for NO, P1-purinoceptors) limit evoked acetylcholine release to prevent overstimulation of the effector cells. These inhibitory mechanisms may also be useful in view of the 100-fold higher affinity of acetylcholine at muscarinic receptors than at nicotinic receptors (muscular type), a property which may facilitate overstimulation.
Wessler
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I
Department of Pharmacology, University of Mainz, Germany.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D009045:Motor Endplate / Q000378:metabolism*; D009451:Neuroeffector Junction / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology
D011976:Receptors, Muscarinic; D000109:Acetylcholine