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• W2013111477 abstract "Adrenomedullin (AM) has two known receptors formed by the calcitonin receptor‐like receptor (CL) and receptor activity‐modifying protein (RAMP) 2 or 3: We report the effects of the antagonist fragments of human AM and CGRP (AM 22–52 and CGRP 8–37 ) in inhibiting AM at human (h), rat (r) and mixed species CL/RAMP2 and CL/RAMP3 receptors transiently expressed in Cos 7 cells or endogenously expressed as rCL/rRAMP2 complexes by Rat 2 and L6 cells. AM 22–52 (10 μ M ) antagonised AM at all CL/RAMP2 complexes (apparent p A 2 values: 7.34±0.14 (hCL/hRAMP2), 7.28±0.06 (Rat 2), 7.00±0.05 (L6), 6.25±0.17 (rCL/hRAMP2)). CGRP 8–37 (10 μ M ) resembled AM 22–52 except on the rCL/hRAMP2 complex, where it did not antagonise AM (apparent p A 2 values: 7.04±0.13 (hCL/hRAMP2), 6.72±0.06 (Rat2), 7.03±0.12 (L6)). On CL/RAMP3 receptors, 10 μ M CGRP 8–37 was an effective antagonist at all combinations (apparent p A 2 values: 6.96±0.08 (hCL/hRAMP3), 6.18±0.18 (rCL/rRAMP3), 6.48±0.20 (rCL/hRAMP3)). However, 10 μ M AM 22–52 only antagonised AM at the hCL/hRAMP3 receptor (apparent p A 2 6.73±0.14). BIBN4096BS (10 μ M ) did not antagonise AM at any of the receptors. Where investigated (all‐rat and rat/human combinations), the agonist potency order on the CL/RAMP3 receptor was AM∼ β CGRP> α CGRP. rRAMP3 showed three apparent polymorphisms, none of which altered its coding sequence. This study shows that on CL/RAMP complexes, AM 22–52 has significant selectivity for the CL/RAMP2 combination over the CL/RAMP3 combination. On the mixed species receptor, CGRP 8–37 showed the opposite selectivity. Thus, depending on the species, it is possible to discriminate pharmacologically between CL/RAMP2 and CL/RAMP3 AM receptors. British Journal of Pharmacology (2003) 140 , 477–486. doi: 10.1038/sj.bjp.0705472" @default.
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• W2013111477 date "2003-10-01" @default.
• W2013111477 modified "2023-10-17" @default.
• W2013111477 title "CL/RAMP2 and CL/RAMP3 produce pharmacologically distinct adrenomedullin receptors: a comparison of effects of adrenomedullin_22-52 , CGRP_8-37 and BIBN4096BS" @default.
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• W2013111477 doi "https://doi.org/10.1038/sj.bjp.0705472" @default.
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