Article date: October 1993
By: Ikuko Kimura, Hiroshi Tsuneki, Katsuya Dezaki, Masayasu Kimura, in Volume 110, Issue 2, pages 639-644
The involvement of calcitonin gene‐related peptide (CGRP) in the mechanism of nicotinic acetylcholine receptor‐operated noncontractile Ca2+ mobilization (not accompanied by twitch tension) was investigated by measuring Ca2+‐aequorin luminescence at the neuromuscular junction of mouse diaphragm muscle treated with neostigmine.
Noncontractile Ca2+ transients were enhanced by 4‐aminopyridine (100 μm), a K+ channel blocker, and inhibited by botulinum toxin (1–100 μg, i.p.) and hexamethonium (10–100 μm), a neuronal nicotinic receptor antagonist.
Noncontractile Ca2+ transients were diminished by CGRP8–37 (10–20 μm), a CGRP antagonist. CGRP (0.3–10 nm) prolonged the duration of noncontractile Ca2+ transients. The effect of CGRP was suppressed by CGRP8_37 (0.1 μm).
Noncontractile Ca2+ transients were inhibited by H‐89 (0.1–1 μm), a protein kinase‐A inhibitor. The catalytic subunit of protein kinase‐A and AA373 (300 μm), a protein kinase‐A activator, prolonged the duration of noncontractile transients. The prolongations either by CGRP or by AA373 were not observed in the presence of H‐89 (0.1 μm).
Contractile (accompanied by twitch tension) but not noncontractile Ca2+ transients were decreased by 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA, 0.3–1 μm), a protein kinase‐C activator. Phospholipase A2 increased only contractile Ca2+ transients. Calmodulin‐related agents affected neither type of Ca2+ transients.
These results provide the first evidence that nicotinic acetylcholine receptor‐operated noncontractile Ca2+ mobilization is promoted by nerve‐released CGRP activating protein kinase‐A, and is dependent on the accumulated amounts of acetylcholine at the neuromuscular junction where desensitization might readily develop.
The involvement of calcitonin gene‐related peptide (CGRP) in the mechanism of nicotinic acetylcholine receptor‐operated noncontractile Ca2+ mobilization (not accompanied by twitch tension) was investigated by measuring Ca2+‐aequorin luminescence at the neuromuscular junction of mouse diaphragm muscle treated with neostigmine.
Noncontractile Ca2+ transients were enhanced by 4‐aminopyridine (100 μm), a K+ channel blocker, and inhibited by botulinum toxin (1–100 μg, i.p.) and hexamethonium (10–100 μm), a neuronal nicotinic receptor antagonist.
Noncontractile Ca2+ transients were diminished by CGRP8–37 (10–20 μm), a CGRP antagonist. CGRP (0.3–10 nm) prolonged the duration of noncontractile Ca2+ transients. The effect of CGRP was suppressed by CGRP8_37 (0.1 μm).
Noncontractile Ca2+ transients were inhibited by H‐89 (0.1–1 μm), a protein kinase‐A inhibitor. The catalytic subunit of protein kinase‐A and AA373 (300 μm), a protein kinase‐A activator, prolonged the duration of noncontractile transients. The prolongations either by CGRP or by AA373 were not observed in the presence of H‐89 (0.1 μm).
Contractile (accompanied by twitch tension) but not noncontractile Ca2+ transients were decreased by 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA, 0.3–1 μm), a protein kinase‐C activator. Phospholipase A2 increased only contractile Ca2+ transients. Calmodulin‐related agents affected neither type of Ca2+ transients.
These results provide the first evidence that nicotinic acetylcholine receptor‐operated noncontractile Ca2+ mobilization is promoted by nerve‐released CGRP activating protein kinase‐A, and is dependent on the accumulated amounts of acetylcholine at the neuromuscular junction where desensitization might readily develop.
DOI: 10.1111/j.1476-5381.1993.tb13859.x
View this article