Somatostatin receptor subtype expression and function in human vascular tissue.
In animal models the somatostatin analog angiopeptin inhibits intimal hyperplasia by acting primarily through somatostatin receptor 2 (SSTR-2). However, the results of clinical trials using angiopeptin have been disappointing. In this study we showed that human blood vessels express high levels of SSTR-1 with significantly lower levels of SSTR-2 and -4. Samples of normal veins and arteries, as well as atherosclerotic arteries, expressed predominantly SSTR-1. In addition, the levels of SSTR-1 varied between individuals, indicating that the vascular disease process may have affected SSTR gene expression. Immunocytochemical studies demonstrated that SSTR-1 was present in endothelial but not vascular smooth muscle cells. No evidence of SSTR-3 or -5 expression was detected in normal or diseased blood vessels. Two endothelial cell preparations, ECV304 and human umbilical vein endothelial cells, were investigated and shown to express only SSTR-1 and -4. Exposure of these cells to 10 nM somatostatin or 10 nM SSTR-1-specific agonist resulted in alterations to the actin cytoskeleton, as characterized by a loss of actin stress fibers coupled with an increase in lamellipodia formation at the plasma membrane. These results suggest that the lack of effectiveness of angiopeptin in humans may be due to the differential expression of SSTR-1 by human endothelial cells.
Curtis
S B
SB
Department of Surgery, University of British Columbia, Vancouver, Canada.
Hewitt
J
J
Yakubovitz
S
S
Anzarut
A
A
Hsiang
Y N
YN
Buchan
A M
AM
D001161:Arteriosclerosis / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D017481:Receptors, Somatostatin / Q000378:metabolism / Q000502:physiology*; D012016:Reference Values; D013004:Somatostatin / Q000494:pharmacology
D006728:Hormones; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; D013004:Somatostatin