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Calcitonin gene-related peptide stimulates proliferation of human endothelial cells

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
;  [1];  [2];  [3];  [4]
  1. Karolinska Institute, Stockholm (Sweden)
  2. Karolinska Institute, Stockholm (Sweden) Karolinska Hospital, Stockholm (Sweden)
  3. Huddinge University Hospital (Sweden)
  4. Karolinska Hospital, Stockholm (Sweden)
The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. {sup 125}I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. The authors thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physicological and pathophysiological events such as ischemia, inflammation, and wound healing.
OSTI ID:
5451074
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:9; ISSN 0027-8424; ISSN PNASA
Country of Publication:
United States
Language:
English

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