Vasodilatory effect of adrenomedullin in mouse aorta.
Human adrenomedullin (AM) and human calcitonin gene-related peptide (CGRP) produced a concentration-dependent relaxation in mouse aorta, precontracted with noradrenaline. EC(50) values for AM and CGRP were 9.8 +/- 2.4 and 4.2 +/- 0.1 nmol/l, respectively. AM-mediated vasorelaxation was partially (3-fold) shifted by AM(22-52), the C-terminal AM fragment, but not by CGRP(8-37), a selective CGRP1 antagonist. Both AM(22-52) and CGRP(8-37) failed to inhibit CGRP-mediated vasorelaxation of mouse aorta rings. Binding of rat [(125)I]AM to these membranes was specific. Both human AM and AM(22-52) displaced rat [(125)I]AM binding in a concentration-dependent manner with IC(50) values of 12.0 +/- 4 and 19.4 +/- 8 nmol/l, respectively. In contrast, both human CGRP and CGRP(8-37) were weak in displacing [(125)I]AM binding. Very little specific binding was observed with [(125)I]CGRP. In conclusion, the data presented here demonstrate that the mouse aorta displays AM receptors that mediate vasorelaxation.
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA. Daryl_J_Ashton@sbphrd.com
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Ashton
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Hieble
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Gout
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Aiyar
D053607:Adrenomedullin; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D011869:Radioligand Assay; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin