[Possible trophic role on the neuromuscular junction of a neuropeptide co-existing with acetylcholine in motor neurons of the spinal cord].
The Calcitonin-Gene Related Peptide (CGRP), a neuropeptide present in chick spinal cord motoneurons, increases the levels of surface acetylcholine receptor (AChR) and of the AChR alpha-subunit mRNA in cultured chick myotubes. Cholera toxin (CT), an activator of adenylate cyclase, produces a similar effect which does not add up with that of CGRP. Consistent with this observation, CGRP increases the content of cyclic AMP in chick muscle cells in culture. Tetrodotoxin (TTX), a blocker of voltage-sensitive Na+ channels, elevates the levels of AChR and of AChR alpha-subunit mRNA. This effect is additive with that of CGRP or CT. TPA (12-O-tetradecanoyl phorbol-13-acetate), an activator of protein kinase C, decreases the level of AChR but has no effect on the level of AChR alpha-subunit mRNA. Interestingly, TPA inhibits the increase of AChR alpha-subunit mRNA caused by TTX without affecting that produced by CGRP or CT. These data suggest that CGRP, which coexists with acetylcholine in spinal cord motoneurons, could be one of the anterograde factors (or a model of such factor) responsible for the enhanced expression of the genes coding for AChR subunits in subneural nuclei, via the activation of adenylate cyclase. Muscle electrical activity would then inhibit the expression of the same genes in extrajunctional nuclei, via another intracellular pathway.
Fontaine
B
B
UA CNRS 041149, Institut Pasteur, Département des Biotechnologies, Paris.
Klarsfeld
A
A
Laufer
R
R
Hökfelt
T
T
Changeux
J P
JP
D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D002642:Chick Embryo; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D009046:Motor Neurons / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000235:genetics; D013116:Spinal Cord / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D009479:Neuropeptides; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D013779:Tetrodotoxin; D002772:Cholera Toxin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate
Rôle trophique possible sur la jonction neuromusculaire d'un neuropeptide coexistant avec l'acétylcholine dans les neurones moteurs de la moelle épinière.