Endothelin-converting-enzyme 1 inhibition and CGRP receptor recycling in human coronary and middle meningeal arteries

  • S Labruijere
  • R De Vries
  • AHJ Danser
  • GS Cottrell
  • A MaassenVanDenBrink
Open Access
Poster presentation

Keywords

Public Health Peptide Internal Medicine Response Curve Calcitonin 

Although best known for its role in the conversion of big endothelin to endothelin-1, endothelin-converting enzyme 1 (ECE-1) also regulates the resensitization of certain neuropeptide receptors, including the receptor for calcitonin gene-related peptide (CGRP) (Padilla et al., 2007). We investigated the role of ECE-1 in the resensitization of responses to CGRP in human coronary (HCA) and middle meningeal (HMA) arteries using the potent and selective ECE-1 inhibitor, SM-19712. Segments of HCA (Ø 0.5–1 mm) and HMA (Ø 0.5–1 mm) were mounted in organ baths and concentration response curves (CRCs) to CGRP were constructed in the absence or presence of the ECE-1 inhibitor SM-19712. After the first CRC to CGRP the segments were washed and after 30-45 minutes a second CRC was constructed in the absence or presence of SM-19712 to investigate ECE-1-dependent CGRP resensitization. Furthermore, CRCs to big endothelin were constructed in the presence or absence of SM-19712. In both HCA and HMA, no differences were seen between the initial responses to CGRP in the absence or presence of SM-19712 (HCA Emax+SM19712 94± 8%, Emax SM19712 93± 5%; pEC50+SM19712 9.1± 0.2, pEC50-SM19712 9.2± 0.1; HMA Emax+SM19712 72± 7%, Emax SM19712 59± 7%; pEC50+SM19712 8.5± 0.4, pEC50-SM19712 8.1± 0.8), as well as between the second CRCs to CGRP in the absence or presence of SM-19712 (HCA Emax+SM19712 110± 13%, Emax SM19712 78± 22%; pEC50+SM19712 7.5± 0.5, pEC50-SM19712 7.9± 0.01; HMA Emax+SM19712 38± 13%, Emax SM19712 44± 1%; pEC50+SM19712 8.6± 0.5, pEC50-SM19712 7.8± 0.9). Furthermore, contractions to big endothelin were not different in the absence or presence of SM-19712 in either HCA (Emax+SM19712 118± 14%, Emax-SM19712 115± 32%; pEC50+SM19712 6.0± 0.5, pEC50-SM19712 6.9± 0.2) or HMA (Emax+SM19712 121± 1%, Emax SM19712 147± 19%; pEC50 SM19712 7.4± 0.4, pEC50+SM19712 7.0± 0.8). Our results indicate that ECE-1 does not regulate the resensitization of CGRP responses in HCA and HMA.

References

  1. 1.
    Padilla BE, et al.: Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and beta-arrestins. J Cell Biol 2007, 179(5):981–97. 10.1083/jcb.200704053PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Labruijere et al; licensee Springer. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • S Labruijere
    • 1
  • R De Vries
    • 1
  • AHJ Danser
    • 1
  • GS Cottrell
    • 2
  • A MaassenVanDenBrink
    • 1
  1. 1.Netherlands
  2. 2.Netherlands

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