Responses to human CGRP, ADM, and PAMP in human thymic arteries

Hunter C. Champion, Trinity J. Bivalacqua, Robert L. Pierce, William A. Murphy, David H. Coy, Albert L. Hyman, Philip J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Responses to human CGRP, adrenomedullin (ADM), and proadrenomedullin NH2-terminal 20 peptide (PAMP) were studied in small human thymic arteries. CGRP, ADM, and PAMP produced concentration-dependent vasodilator responses in arteries preconstricted with the thromboxane mimic U-46619. Responses to ADM and PAMP were attenuated, whereas responses to CGRP were not altered by endothelial denudation. Inhibitors of nitric oxide synthase and guanylyl cyclase attenuated responses to ADM and PAMP but not to CGRP. The CGRP1 receptor antagonist CGRP(8-37) attenuated responses to CGRP and ADM but not to PAMP. Responses to CGRP were reduced by SQ-22536 and Rp-cAMPS, inhibitors of adenylyl cyclase and PKA. These data suggest that responses to CGRP and ADM are mediated by CGRP(8-37)-sensitive receptors and that the endothelial ADM receptor induces vasodilation by a nitric oxide-guanylyl cyclase mechanism, whereas a smooth muscle CGRP receptor signals by a cAMP-dependent mechanism. A different endothelial receptor recognizes PAMP and signals by a nitric oxide-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)R531-R537
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume284
Issue number2 53-2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

Keywords

  • CGRP1 receptor
  • Human thymus
  • Vascular endothelium
  • Vascular tone

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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