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Enhancement by calcitonin gene‐related peptide of non‐contractile Ca 2+ ‐induced nicotinic receptor desensitization at the mouse neuromuscular junction
Author(s) -
Dezaki Katsuya,
Kimura Ikuko,
Tsuneki Hiroshi,
Kimura Masayasu
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15632.x
Subject(s) - medicine , endocrinology , calcitonin gene related peptide , muscle contraction , contraction (grammar) , staurosporine , chemistry , receptor , biology , protein kinase c , neuropeptide , signal transduction , biochemistry
1 Nicotinic acetylcholine receptor (AChR)‐operated non‐contractile Ca 2+ mobilization (unaccompanied by muscle contraction) depressed contractile Ca 2+ mobilization (accompanied by muscle contraction) in mouse diaphragm muscles. In the process of nicotinic AChR desensitization, the enhancing role of calcitonin gene‐related peptide (CGRP) on the non‐contractile Ca 2+ ‐induced depression of contractile Ca 2+ mobilization was investigated by measurement of Ca 2+ ‐aequorin luminescence in the presence of neostigmine (0.1 μ m ). 2 When the phrenic nerve was stimulated with paired pulses at intervals of 150, 300, 600, 1000 and 2000 ms, contractile Ca 2+ transients were elicited during the generation of non‐contractile Ca 2+ mobilization. The amplitude of the contractile Ca 2+ transients elicited by the second pulse (S 2 ) was depressed at the shorter pulse intervals, but not at the longer pulse intervals. 3 The extent of depression of S 2 was enhanced when the duration of non‐contractile Ca 2+ mobilization was prolonged by CGRP (10 nM). However, CGRP failed to enhance the depression of S 2 when non‐contractile Ca 2+ mobilization was not observed at the low external Ca 2+ concentration (1.3 mM). 4 The enhancing effect by CGRP on the depression of S 2 was counteracted by staurosporine (3 nM), a protein kinase‐C inhibitor, despite prolongation of the duration of non‐contractile Ca 2+ mobilization. 5 When H‐89 (1 μ m ), a protein kinase‐A inhibitor, completely blocked non‐contractile Ca 2+ mobilization, the depression of S 2 was diminished. The prolongation of the duration of non‐contractile Ca 2+ mobilization by AA373 (300 μ m ), a protein kinase‐A activator, enhanced the depression of S 2 . The enhancing effect was observed neither with CGRP nor with AA373, in the presence of H‐89 (0.1 μ m ). 6 These findings suggest that the CGRP mobilizes non‐contractile Ca 2+ through activation of protein kinase‐A, which in turn may activate protein kinase‐C, then enhance the desensitization of postsynaptic nicotinic AChRs at the neuromuscular junction.