Paracrine stimulation of cell growth by cholecystokinin/gastrin through cholecystokinin-B receptor on GH3 cells in vitro.
Cholecystokinin (CCK) is detected in pituitary tumors but its role remains unknown. On the hypothesis that CCK may facilitate the cell growth in pituitary tumors, we have examined the effect of CCK on cell growth using a rat pituitary tumor cell line, GH3, cultured in a serum-free, chemically defined medium. Addition of sulfated CCK-(26-33) (CCK-8) in two different concentrations (0.5 approximately 1 nM) caused a significant increase in the number of GH3 cells. The antagonist (1 microM) for CCK-B receptor, but not CCK-A receptor, significantly inhibited the number of GH3 cells. Northern blot analysis revealed a significant expression of CCK-B receptor mRNA in GH3 cells, but not in normal rat pituitary glands. In addition, immunoreactive CCK/gastrin was detected by RIA in the GH3 cell extracts as well as the serum-free culture medium. In GH3 cell extracts, both CCK-8 and gastrin like peptides were identified by gel chromatography. These findings provided the first evidence for an autocrine/paracrine role of CCK and gastrin on stimulation of GH3 cell growth through the CCK-B receptor.
Department of Medicine, Kobe University School of Medicine, Japan.
Y
Y
Xu
H
H
Kaji
Y
Y
Okimura
T
T
Matsui
H
H
Abe
K
K
Chihara
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology*; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011863:Radioimmunoassay; D051381:Rats; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D005755:Gastrins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin