Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX

Research output: Contribution to journalJournal articleResearchpeer-review

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Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX. / Sheykhzade, Majid; Abdolalizadeh, Bahareh; Koole, Cassandra; Pickering, Darryl S; Dreisig, Karin; Johansson, Sara Ellinor; Abboud, Balsam Kadri; Dreier, Rasmus; Berg, Jais Oliver; Jeppesen, Jørgen Lykke; Sexton, Patrick; Edvinsson, Lars; Wootten, Denise; Sams, Anette.

In: European Journal of Pharmacology, Vol. 829, 2018, p. 85-92.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Sheykhzade, M, Abdolalizadeh, B, Koole, C, Pickering, DS, Dreisig, K, Johansson, SE, Abboud, BK, Dreier, R, Berg, JO, Jeppesen, JL, Sexton, P, Edvinsson, L, Wootten, D & Sams, A 2018, 'Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX', European Journal of Pharmacology, vol. 829, pp. 85-92. https://doi.org/10.1016/j.ejphar.2018.04.007

APA

Sheykhzade, M., Abdolalizadeh, B., Koole, C., Pickering, D. S., Dreisig, K., Johansson, S. E., ... Sams, A. (2018). Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX. European Journal of Pharmacology, 829, 85-92. https://doi.org/10.1016/j.ejphar.2018.04.007

Vancouver

Sheykhzade M, Abdolalizadeh B, Koole C, Pickering DS, Dreisig K, Johansson SE et al. Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX. European Journal of Pharmacology. 2018;829:85-92. https://doi.org/10.1016/j.ejphar.2018.04.007

Author

Sheykhzade, Majid ; Abdolalizadeh, Bahareh ; Koole, Cassandra ; Pickering, Darryl S ; Dreisig, Karin ; Johansson, Sara Ellinor ; Abboud, Balsam Kadri ; Dreier, Rasmus ; Berg, Jais Oliver ; Jeppesen, Jørgen Lykke ; Sexton, Patrick ; Edvinsson, Lars ; Wootten, Denise ; Sams, Anette. / Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX. In: European Journal of Pharmacology. 2018 ; Vol. 829. pp. 85-92.

Bibtex

@article{410a892820924e3a887fd859733faea0,
title = "Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX",
abstract = "The purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and SAX, a metabolically stable CGRP analog, in isolated rat and human artery segments (vasoactivity), in recombinant human CGRP receptors (cAMP accumulation), and in native rat receptors (receptor binding).Vasodilatory potencies (pEC50) of SAX and CGRP in isolated rat mesenteric artery were 8.2 ± 0.12 and 9.0 ± 0.11 and the CGRP receptor antagonist BIBN4096BS competitively inhibited the vasodilatory effects of SAX and CGRP with potencies (pA2) of 7.6 ± 0.13 and 8.0 ± 0.16. mRNAs encoding CGRP receptors (CLR and RAMP1) were expressed in the artery. In rat cerebral membranes, binding affinities (pKi) of SAX and CGRP were 8.3 ± 0.19 and 9.3 ± 0.14.In human subcutaneous artery, SAX and CGRP induced vasodilation (pEC50 8.8 ± 0.18 and 9.5 ± 0.13), while pEC50s for cAMP production by human recombinant receptors were 9.1 ± 0.16 and 10.2 ± 0.19. Here, pA2 values of BIBN4096BS were 10.5 ± 0.24 and 11.1 ± 0.32. The presence of albumin caused a selective 10-fold reduction in potency and binding affinity of SAX.In conclusion, SAX and CGRP act on a uniform BIBN4096BS sensitive receptor population in our experiments and the potency of SAX is 5-10 fold lower than that of CGRP.",
author = "Majid Sheykhzade and Bahareh Abdolalizadeh and Cassandra Koole and Pickering, {Darryl S} and Karin Dreisig and Johansson, {Sara Ellinor} and Abboud, {Balsam Kadri} and Rasmus Dreier and Berg, {Jais Oliver} and Jeppesen, {J{\o}rgen Lykke} and Patrick Sexton and Lars Edvinsson and Denise Wootten and Anette Sams",
year = "2018",
doi = "10.1016/j.ejphar.2018.04.007",
language = "English",
volume = "829",
pages = "85--92",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX

AU - Sheykhzade, Majid

AU - Abdolalizadeh, Bahareh

AU - Koole, Cassandra

AU - Pickering, Darryl S

AU - Dreisig, Karin

AU - Johansson, Sara Ellinor

AU - Abboud, Balsam Kadri

AU - Dreier, Rasmus

AU - Berg, Jais Oliver

AU - Jeppesen, Jørgen Lykke

AU - Sexton, Patrick

AU - Edvinsson, Lars

AU - Wootten, Denise

AU - Sams, Anette

PY - 2018

Y1 - 2018

N2 - The purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and SAX, a metabolically stable CGRP analog, in isolated rat and human artery segments (vasoactivity), in recombinant human CGRP receptors (cAMP accumulation), and in native rat receptors (receptor binding).Vasodilatory potencies (pEC50) of SAX and CGRP in isolated rat mesenteric artery were 8.2 ± 0.12 and 9.0 ± 0.11 and the CGRP receptor antagonist BIBN4096BS competitively inhibited the vasodilatory effects of SAX and CGRP with potencies (pA2) of 7.6 ± 0.13 and 8.0 ± 0.16. mRNAs encoding CGRP receptors (CLR and RAMP1) were expressed in the artery. In rat cerebral membranes, binding affinities (pKi) of SAX and CGRP were 8.3 ± 0.19 and 9.3 ± 0.14.In human subcutaneous artery, SAX and CGRP induced vasodilation (pEC50 8.8 ± 0.18 and 9.5 ± 0.13), while pEC50s for cAMP production by human recombinant receptors were 9.1 ± 0.16 and 10.2 ± 0.19. Here, pA2 values of BIBN4096BS were 10.5 ± 0.24 and 11.1 ± 0.32. The presence of albumin caused a selective 10-fold reduction in potency and binding affinity of SAX.In conclusion, SAX and CGRP act on a uniform BIBN4096BS sensitive receptor population in our experiments and the potency of SAX is 5-10 fold lower than that of CGRP.

AB - The purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and SAX, a metabolically stable CGRP analog, in isolated rat and human artery segments (vasoactivity), in recombinant human CGRP receptors (cAMP accumulation), and in native rat receptors (receptor binding).Vasodilatory potencies (pEC50) of SAX and CGRP in isolated rat mesenteric artery were 8.2 ± 0.12 and 9.0 ± 0.11 and the CGRP receptor antagonist BIBN4096BS competitively inhibited the vasodilatory effects of SAX and CGRP with potencies (pA2) of 7.6 ± 0.13 and 8.0 ± 0.16. mRNAs encoding CGRP receptors (CLR and RAMP1) were expressed in the artery. In rat cerebral membranes, binding affinities (pKi) of SAX and CGRP were 8.3 ± 0.19 and 9.3 ± 0.14.In human subcutaneous artery, SAX and CGRP induced vasodilation (pEC50 8.8 ± 0.18 and 9.5 ± 0.13), while pEC50s for cAMP production by human recombinant receptors were 9.1 ± 0.16 and 10.2 ± 0.19. Here, pA2 values of BIBN4096BS were 10.5 ± 0.24 and 11.1 ± 0.32. The presence of albumin caused a selective 10-fold reduction in potency and binding affinity of SAX.In conclusion, SAX and CGRP act on a uniform BIBN4096BS sensitive receptor population in our experiments and the potency of SAX is 5-10 fold lower than that of CGRP.

U2 - 10.1016/j.ejphar.2018.04.007

DO - 10.1016/j.ejphar.2018.04.007

M3 - Journal article

VL - 829

SP - 85

EP - 92

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -

ID: 193173387