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Greenberg, Harry Z. E., Jahan, Kazi S., Shi, Jian, Ho, W. S. Vanessa and Albert, Anthony P. 
ORCID: https://orcid.org/0000-0002-3596-9634
(2016)
The calcilytics Calhex-231 and NPS 2143 and the calcimimetic Calindol reduce vascular reactivity via inhibition of voltage-gated Ca2+channels.
European Journal of Pharmacology, 791.
pp. 659-668.
ISSN 0014-2999
Abstract
The present study investigates the effect of commonly used negative and positive allosteric modulators of the calcium-sensing receptor (CaSR) on vascular reactivity. In wire myography studies, increasing [Ca2+]ofrom 1 mM to 6 mM induced concentration-dependent relaxations of methoxamine-induced pre-contracted rabbit mesenteric arteries, with 6 mM [Ca2+]oproducing almost complete relaxation. [Ca2+]o-induced relaxations were attenuated in the presence of the calcilytics Calhex-231 and NPS 2143, and abolished by the removal of the endothelium. In addition to their calcilytic effects, Calhex-231 and NPS 2143 also produced concentration-dependent inhibitions of methoxamine- or KCl-induced precontracted tone, which were unaffected by removal of the endothelium and unopposed in the presence of the calcimimetic Calindol. In vessels with depleted Ca2+stores, contractions mediated by Ca2+influx via voltage-gated Ca2+channels (VGCCs) were inhibited by Calhex231. In freshly isolated single rabbit mesenteric artery smooth muscle cells, Calhex-231 and NPS 2143 inhibited whole-cell VGCC currents. Application of Calindol also inhibited methoxamine- and KCl-induced pre-contracted tone, and inhibited whole-cell VGCC currents. In conclusion, in addition to their CaSR-mediated actions in the vasculature, Calhex-231, NPS 2143 and Calindol reduce vascular contractility via direct inhibition of VGCCs.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by a British Heart Foundation, UK Ph.D. Studentship for H. Z. E. Greenberg ( FS/13/10/30021 to A.P.A); and by the Biotechnology and Biological Sciences Research Council , UK ( BB/J007226/1 to A.P.A). Publisher Copyright: © 2016 |
| Uncontrolled Keywords: | calcilytic,calcimimetic,calcium-sensing receptor,calhex-231,calindol,nps 2143,pharmacology ,/dk/atira/pure/subjectarea/asjc/3000/3004 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Oct 2024 09:30 |
| Last Modified: | 03 Nov 2024 07:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97248 |
| DOI: | 10.1016/j.ejphar.2016.10.008 |
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