Calcitonin gene-related peptide acts presynaptically to increase quantal size and output at frog neuromuscular junctions

Authors

  • William Van der Kloot,

    1. Department of Physiology and Biophysics and Department of Pharmacological Sciences, Health Sciences Center, State University of New York at Stony Brook, NY 11794-8661, USA
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  • William B. Benjamin,

    1. Department of Physiology and Biophysics and Department of Pharmacological Sciences, Health Sciences Center, State University of New York at Stony Brook, NY 11794-8661, USA
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  • Olga P. Balezina

    1. Department of Physiology and Biophysics and Department of Pharmacological Sciences, Health Sciences Center, State University of New York at Stony Brook, NY 11794-8661, USA
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  • Author's present address

    O. P. Balezina: Department of Human and Animal Physiology, Moscow State University, 119899 Moscow, Russia.

Corresponding author W. Van der Kloot: Department of Physiology, 8661 SUNY, Stony Brook, NY 11794–8661, USA. Email: wvanderkloot@ccmail.sunysb.edu

Abstract

  • 1Calcitonin gene-related peptide (CGRP) is found in dense-cored vesicles in the motor nerve terminal.
  • 2Exogenous 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.)
  • 3The hCGRP effect was not blocked by fragment 8–37, an antagonist of one class of CGRP receptor.
  • 4hCGRP increases evoked quantal output and miniature endplate potential (MEPP) frequency, again by activating PKA.
  • 5CGRP 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.

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