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- Title
The Interaction between Tropomyosin-Related Kinase B Receptors and Presynaptic Muscarinic Receptors Modulates Transmitter Release in Adult Rodent Motor Nerve Terminals.
- Authors
Garcia, Neus; Tomàs, Marta; Santafé, Manel M.; Besalduch, Nuria; Lanuza, Maria A.; Tomàs, Josep
- Abstract
The neurotrophin brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase B (trkB) and p75NTR are present in the nerve terminals on the neuromuscular junctions (NMJs) of the levator auris longus muscle of the adult mouse. Exogenously added BDNF or NT-4 increased evoked ACh release after 3 h. This presynaptic effect (the size of the spontaneous potentials is not affected) is specific because it is not produced by neurotrophin-3 (NT-3) and is prevented by preincubation with trkB-IgG chimera or by pharmacological block of trkB [K-252a (C27H21N3O5)] or p75NTR [Pep5 (C86H111N25O19S2)] signaling. The effect of BDNF depends on the M1 and M2 muscarinic acetylcholine autoreceptors (mAChRs) because it is prevented by atropine, pirenzepine and methoctramine. We found that K-252a incubation reduces ACh release (~50%) in a short time (1 h), but the p75NTR signaling inhibitor Pep5 does not have this effect. The specificity of the K-252a blocking effect on trkB was confirmed with the anti-trkB antibody 47/trkB, which reduces evoked ACh release, like K-252a, whereas the nonpermeant tyrosine kinase blocker K-252b does not. Neither does incubation with the fusion protein trkB-IgG (to chelate endogenous BDNF/NT-4), anti-BDNF or anti-NT-4 change ACh release. Thus, the trkB receptor normally seems to be coupled to ACh release when there is no short-term local effect of neurotrophins at the NMJ. The normal function of the mAChR mechanism is a permissive prerequisite for the trkB pathway to couple to ACh release. Reciprocally, the normal function of trkB modulatesM1- and M2-subtype muscarinic pathways.
- Subjects
NEUROPLASTICITY; TROPOMYOSINS; MUSCARINIC receptors; PROTEIN-tyrosine kinases; NEUROTRANSMITTERS; LABORATORY rodents
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 48, p16514
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2676-10.2010