Calcitonin gene-related peptide acts presynaptically to increase quantal size and output at frog neuromuscular junctions.
1. Calcitonin gene-related peptide (CGRP) is found in dense-cored vesicles in the motor nerve terminal. 2. Exogenous CGRP increased the size of the quanta. The increase in size reached a maximum after about 40 min. The lowest effective concentration of human CGRP (hCGRP) was 0.8 nM. The action of hCGRP was antagonized by (-)-vesamicol, a drug that blocks active acetylcholine (ACh) uptake into synaptic vesicles, so it appears that hCGRP increases size by adding more ACh to the quanta. The action of hCGRP was antagonized by drugs that block the activation of protein kinase A (PKA). (In other preparations CGRP also activates PKA.) 3. The hCGRP effect was not blocked by fragment 8-37, an antagonist of one class of CGRP receptor. 4. hCGRP increases evoked quantal output and miniature endplate potential (MEPP) frequency, again by activating PKA. 5. CGRP release was measured by radioimmunoassay. Release was increased by depolarization with elevated K+, but the amounts released appear to be below those needed to affect quantal size or output. Moreover, although elevated K+ can increase quantal size it acts by a pathway that does not involve PKA. We suggest that the most likely target of endogenously released CGRP is the regulation of circulation of the muscle.
Van der Kloot
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Department of Physiology and Biophysics, Health Sciences Center, State University of New York at Stony Brook, NY 11794-8661, USA. wvanderkloot@ccmail.sunysb.edu
Benjamin
W B
WB
Balezina
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OP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011789:Quantum Theory; D011894:Rana pipiens; D013873:Thionucleotides / Q000494:pharmacology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D013873:Thionucleotides; C058636:calcitonin gene-related peptide (8-37); C016957:adenosine-3',5'-cyclic phosphorothioate; C006189:vesamicol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; C078814:anandamide