Enhancement by calcitonin gene-related peptide of nicotinic receptor-operated noncontractile Ca2+ mobilization at the mouse neuromuscular junction. 1993

I Kimura, and H Tsuneki, and K Dezaki, and M Kimura
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.

1. 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 Ca(2+)-aequorin luminescence at the neuromuscular junction of mouse diaphragm muscle treated with neostigmine. 2. Noncontractile Ca2+ transients were enhanced by 4-aminopyridine (100 microM), a K+ channel blocker, and inhibited by botulinum toxin (1-100 micrograms, i.p.) and hexamethonium (10-100 microM), a neuronal nicotinic receptor antagonist. 3. Noncontractile Ca2+ transients were diminished by CGRP8-37 (10-20 microM), 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 microM). 4. Noncontractile Ca2+ transients were inhibited by H-89 (0.1-1 microM), a protein kinase-A inhibitor. The catalytic subunit of protein kinase-A and AA373 (300 microM), 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 microM). 5. Contractile (accompanied by twitch tension) but not noncontractile Ca2+ transients were decreased by 12-O-tetradecanoyl phorbol 13-acetate (TPA, 0.3-1 microM), a protein kinase-C activator. Phospholipase A2 increased only contractile Ca2+ transients. Calmodulin-related agents affected neither type of Ca2+ transients. 6. 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.

UI MeSH Term Description Entries
D008297 Male Males
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009411 Nerve Endings Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS. Ending, Nerve,Endings, Nerve,Nerve Ending
D009469 Neuromuscular Junction The synapse between a neuron and a muscle. Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D010741 Phospholipases A Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011978 Receptors, Nicotinic One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors. Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002147 Calmodulin A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent

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