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Carlton-Carew, Simonette R. E., Greenberg, Harry Z. E., Greenwood, Iain A. and Albert, Anthony P. 
ORCID: https://orcid.org/0000-0002-3596-9634
(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).
ISSN 2051-817X
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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 |
|---|---|
| Additional Information: | Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding Information: This work was supported by a British Heart Foundation PhD Studentships for H. Z. E. Greenberg (FS/13/10/30021 to A.P.A) and S.R.E.C\u2010C (FS/17/40/32942 to A.P.A); and by the Biotechnology and Biological Sciences Research Council (BB/J007226/1 to A.P.A). |
| Uncontrolled Keywords: | calcitonin gene-related peptide,calcium-sensing receptor,perivascular sensory nerves,substance p,vascular smooth muscle,physiology,physiology (medical) ,/dk/atira/pure/subjectarea/asjc/1300/1314 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 01 Nov 2024 16:30 |
| Last Modified: | 04 Nov 2024 11:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97430 |
| DOI: | 10.14814/phy2.16125 |
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