Carlton-Carew, SRE; Greenberg, HZE; Greenwood, IA; Albert, AP
(2024)
Stimulation of the calcium-sensing receptor induces relaxations through CGRP and NK1 receptor-mediated pathways in male rat mesenteric arteries.
PHYSIOLOGICAL REPORTS, 12 (12).
e16125.
ISSN 2051-817X
https://doi.org/10.14814/phy2.16125
SGUL Authors: Albert, Anthony Paul
Abstract
Stimulation of the calcium-sensing receptor (CaSR) regulates vascular contractility, but cellular mechanisms involved remain unclear. This study investigated the role of perivascular sensory nerves in CaSR-induced relaxations of male rat mesenteric arteries. In fluorescence studies, colocalisation between synaptophysin, a synaptic vesicle marker, and the CaSR was present in the adventitial layer of arterial segments. Using wire myography, increasing external Ca2+ concentration ([Ca2+]o) from 1 to 10 mM induced vasorelaxations, previously shown to involve the CaSR, which were inhibited by pretreatment with capsaicin. [Ca2+]o-induced vasorelaxations were partially reduced by the calcitonin gene-related peptide (CGRP) receptor blockers, CGRP 8–37 and BIBN 4096, and the neurokinin 1 (NK1) receptor blocker L733,060. The inhibitory effect of CGRP 8–37 required a functional endothelium whereas the inhibitory action of L733,060 did not. Complete inhibition of [Ca2+]o-induced vasorelaxations occurred when CGRP 8–37 and L733,060 were applied together. [Ca2+]o-induced vasorelaxations in the presence of capsaicin were abolished by the ATP-dependent K+ channel (KATP) blocker PNU 37883, but unaffected by the endothelium nitric oxide synthase (eNOS) inhibitor L-NAME. We suggest that the CaSR on perivascular sensory nerves mediate relaxations in rat mesenteric arteries via endothelium-dependent and -independent mechanisms involving CGRP and NK1 receptor-activated NO production and KATP channels, respectively.
Item Type: |
Article
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Additional Information: |
© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: |
calcitonin gene-related peptide, calcium-sensing receptor, perivascular sensory nerves, substance P, vascular smooth muscle, 0606 Physiology, 1103 Clinical Sciences, 1116 Medical Physiology |
SGUL Research Institute / Research Centre: |
Academic Structure > REF 2021 user group |
Journal or Publication Title: |
PHYSIOLOGICAL REPORTS |
ISSN: |
2051-817X |
Dates: |
Date | Event |
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20 June 2024 | Published | 14 June 2024 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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Web of Science ID: |
WOS:001251614600001 |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/116632 |
Publisher's version: |
https://doi.org/10.14814/phy2.16125 |
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