Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX
Research output: Contribution to journal › Journal article › Research › peer-review
Majid Sheykhzade, Bahareh Abdolalizadeh, Cassandra Koole, Darryl S Pickering, Karin Dreisig, Sara Ellinor Johansson, Balsam Kadri Abboud, Rasmus Dreier, Jais Oliver Berg, Jørgen Lykke Jeppesen, Patrick Sexton, Lars Edvinsson, Denise Wootten, Anette Sams
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.
|Journal||European Journal of Pharmacology|
|Publication status||Published - 2018|