Calcitonin gene-related peptide potentiates nicotinic acetylcholine receptor-operated slow Ca2+ mobilization at mouse muscle endplates.
1. The involvement of calcitonin gene-related peptide (CGRP) in the non-contractile slow Ca2+ mobilization induced by prolonged nicotinic stimulation was investigated by measurement of [Ca2+], levels in mouse single muscle cells (flexor digitorum brevis; FDB) loaded with a Ca2+ indicator fluo-3 using confocal laser scanning microscopy. 2. CGRP (3-30 nM) potentiated acetylcholine (ACh, 1 microM)-elicited slow Ca2+ mobilization in a concentration-dependent manner. 3. The potentiation by CGRP of the slow Ca2+ component was greatly depressed by a competitive nicotinic antagonist (+)-tubocurarine (5 microM). The Ca2+ channel blocker nitrendipine (1 microM) affected neither ACh responses nor the CGRP potentiation. 4. The slow Ca2+ component was completely abolished by reducing [Ca2+]0 from 2.5 to 0.25 mM whereas the fast component was not affected. The CGRP-induced potentiation of slow Ca2+ signal was also depressed by decreasing [Ca2+]0. 5. Isoproterenol (30 microM) and 8-bromo-adenosine 3',5'-cyclic monophosphate (1 mM) potentiated the ACh-elicited slow Ca2+ response. The potentiation by CGRP of the slow Ca2+ component was completely abolished by a protein kinase-A inhibitor H-89 (1 microM). 6. These findings indicate that CGRP potentiates the nicotinic ACh receptor-operated slow Ca2+ signal via the activation of protein kinase-A system at the skeletal muscle endplates.
Salim
S Y
SY
Department of Pharmacology, Faculty of Medicine, Assiut University, Egypt.
Dezaki
K
K
Tsuneki
H
H
Abdel-Zaher
A O
AO
Kimura
I
I
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction; D014403:Tubocurarine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009568:Nitrendipine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol; D002118:Calcium; D014403:Tubocurarine