CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles
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CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles. / Le, Thi Lisa; Jagd Grell, Anne-Sofie; Sheykhzade, Majid; Warfvinge, Karin; Edvinsson, Lars; Sams, Anette.
In: European Journal of Pharmacology, Vol. 875, 173033, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles
AU - Le, Thi Lisa
AU - Jagd Grell, Anne-Sofie
AU - Sheykhzade, Majid
AU - Warfvinge, Karin
AU - Edvinsson, Lars
AU - Sams, Anette
N1 - Copyright © 2020. Published by Elsevier B.V.
PY - 2020
Y1 - 2020
N2 - CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC100 value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC100 values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC100 peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.
AB - CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC100 value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC100 values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC100 peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.
U2 - 10.1016/j.ejphar.2020.173033
DO - 10.1016/j.ejphar.2020.173033
M3 - Journal article
C2 - 32097658
VL - 875
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
M1 - 173033
ER -
ID: 237044410