Receptor‐mediated autocrine growth‐stimulatory effect of 5‐hydroxytryptamine on cultured human pancreatic carcinoid cells
作者:
Jin Ishizuka,
R. Daniel Beauchamp,
Courtney M. Townsend,
George H. Greeley,
James C. Thompson,
期刊:
Journal of Cellular Physiology
(WILEY Available online 1992)
卷期:
Volume 150,
issue 1
页码: 1-7
ISSN:0021-9541
年代: 1992
DOI:10.1002/jcp.1041500102
出版商: Wiley Subscription Services, Inc., A Wiley Company
数据来源: WILEY
摘要:
Abstract5‐hydroxytryptamine (5‐HT) is a mitogen for fibroblasts, vascular smooth muscle cells, renal mesangial cells, and jejunal crypt cells. The human carcinoid cell line (termed BON) that we established in our laboratory from a pancreatic carcinoid tumor produces and secretes 5‐HT. In this study, therefore, we examined the effect of 5‐HT on growth of BON cells. Furthermore, by use of selective 5‐HT receptor antagonists, we examined receptor and post‐receptor mechanisms by which 5‐HT‐induced responses were produced. 5‐HT stimulated growth of BON cells. 5‐HT stimulated phosphatidylinositol (PI) hydrolysis in a dose‐dependent fashion and inhibited cyclic AMP production in a dose‐dependent fashion. The 5‐HT1A/1Breceptor antagonist, SDZ 21–009, prevented the reduction of cyclic AMP production evoked by 5‐HT and inhibited the mitogenic action of 5‐HT. The 5‐HT1C/2receptor antagonist, mesulergine, competitively inhibited PI hydrolysis, but did not affect the mitogenic action of 5‐HT. The mitogenic action of 5‐HT and the reduction of cyclic AMP production evoked by 5‐HT were also inhibited by pertussis toxin. These results suggest that 5‐HT is an autocrine growth factor for BON cells and that mitogenic mechanism of 5‐HT involves receptor‐mediated toxin‐sensitive GTP binding protein. 8‐bromo‐cyclic AMP inhibited growth of BON cells whereas 8‐bromo‐cyclic GMP had no effect on cell growth. Involvement of protein kinase A in BON cell growth regulation was confirmed by the observation that a cAMP‐dependent protein kin
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