Calcitonin gene-related peptide elevates calcium and polarizes membrane potential in MG-63 cells by both cAMP-independent and -dependent mechanisms

American Journal of Physiology. Cell Physiology
Douglas M BurnsTomoyuki Kawase

Abstract

Published data suggest that the neuropeptide calcitonin gene-related peptide (CGRP) can stimulate osteoblastic bone formation; however, interest has focused on activation of cAMP-dependent signaling pathways in osteogenic cells without full consideration of the importance of cAMP-independent signaling. We have now examined the effects of CGRP on intracellular Ca(2+) concentration ([Ca(2+)](int)) and membrane potential (E(m)) in preosteoblastic human MG-63 cells by single-cell fluorescent confocal analysis using fluo 4-AM-fura red-AM and bis(1,3-dibarbituric acid)-trimethine oxanol [DiBAC(4)(3)] bis-oxonol assays. CGRP produced a two-stage change in [Ca(2+)](int): a rapid transient peak and a secondary sustained increase. Both responses were dose dependent with an EC(50) of approximately 0.30 nM, and the maximal effect (initially approximately 3-fold over basal levels) was observed at 20 nM. The initial phase was sensitive to inhibition of Ca(2+) mobilization with thapsigargin, whereas the secondary phase was eliminated only by blocking transmembrane Ca(2+) influx with verapamil or inhibiting cAMP-dependent signaling with the Rp isomer of adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS). These data suggest that CGRP initia...Continue Reading

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Citations

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Aug 17, 2005·Journal of Neuroendocrinology·J S Kinsey-JonesK T O'Byrne
Mar 6, 2013·Veterinary Clinical Pathology·Qendrim ZebeliBurim N Ametaj
Jun 10, 2010·Journal of Cellular Physiology·Emanuela MrakIsabella Villa
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Dec 13, 2018·Physiological Reviews·Dorit NaotJillian Cornish
Feb 27, 2007·Journal of Materials Science. Materials in Medicine·P ValérioM F Leite
Apr 14, 2006·American Journal of Physiology. Cell Physiology·I VillaF Guidobono
Sep 24, 2020·International Journal of Endocrinology·Jingbo XieQingshan Sun

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