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No Distinct Address and Message Domains Involved in Endothelin‐1/ET A ‐mediated Arterial Contractions
Author(s) -
Compeer Matthijs G,
Meens Merlijn JPMT,
Hackeng Tilman M,
De Mey Jo GR
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.961.6
Subject(s) - calcitonin gene related peptide , chemistry , endothelin receptor , vasomotor , vasodilation , endothelin 1 , endocrinology , medicine , receptor , calcitonin , mesenteric arteries , electrical impedance myography , anatomy , neuropeptide , artery
Objective Many peptidergic GPCR agonists contain distinct binding (address) and activating (message) domains. We evaluated whether this is also the case for the vasomotor effects of calcitonin gene‐related peptide (CGRP) and endothelin‐1 (ET‐1). Methods Contractile and relaxing effects of commercial peptides and locally synthesized loop‐fragments were recorded in 2 nd order rat mesenteric arteries by wire‐myography under conditions excluding the endothelium and the sensory‐motor nerves. Results In arteries contracted by 16 nM ET‐1, 0.1–100nM CGRP1‐37 caused relaxations that were antagonized by 1μM CGRP8‐37; neither effect was modified by 1μM CGRP1‐7. 1–16 nM ET‐1(1–21) caused ET A ‐mediated contractions that were neither mimicked nor antagonized by 1μM Ala 1,3,11,15 ET‐1 (1–21), ET‐1(11–21), ET(16–21) or ET‐1(1–15). Intact ET‐3(1–21) caused contractions of similar amplitude with 30 times lower potency. Conclusion While distinct domains of CGRP take part in its binding and vasodilator effects, both the intact N‐terminal loop and the C‐terminal tail of ET‐1 are required for high affinity binding and activation of vasoconstrictor ET A ‐receptors. This study was performed within the frame of TIPharma project T2‐301.