Effect of cyclic AMP on urokinase-type plasminogen activator receptor and fibrinolytic factors in a human osteoblast-like cell line.
We investigated the effect of cyclic AMP (cAMP) on the pericellular fibrinolytic system in NY cells. Dibutyryl cAMP (dbcAMP) or forskolin increased the level of urokinase-type plasminogen activator (u-PA) mRNA and enhanced the secretion of u-PA antigen into the conditioned medium. These agents also increased u-PA antigen on the cell surface. PA inhibitor-1 (PAI-1) antigen was inhibited by dbcAMP or forskolin. Butyrate had no effect on the production and secretion of u-PA and PAI-1. A binding assay of 125I-DFP-u-PA to NY cells revealed a single class of binding sites with a Kd of 3.85 nM and Bmax of 0.89.10(5) binding sites/cell. The Bmax was increased by dbcAMP (1 mM or 10 mM), forskolin (2 microM or 20 microM) of 1.0-, 1.4-, 1.2- and 1.8-fold, respectively. However, the Kd value was not changed. Furthermore, the level of mRNA for the u-PA receptor (u-PAR) was increased by these agents 1.2-, 1.7-, 1.8- and 2.5-fold, respectively. However, butyrate did not alter either the Bmax or the u-PAR mRNA level. These results indicated that the pericellular fibrinolytic activity induced by u-PA/u-PAR is modulated by cAMP in osteoblast-like cells.
Nonaka
T
T
Department of Physiology, Kinki University of Medicine, Osakasayama, Japan.
Matsumoto
H
H
Shimada
W
W
Miyagi
I
I
Okada
K
K
Fukao
H
H
Ueshima
S
S
Kikuchi
H
H
Tanaka
S
S
Matsuo
O
O
D003994:Bucladesine / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002460:Cell Line / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D002087:Butyrates; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D020148:Butyric Acid; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D014568:Urokinase-Type Plasminogen Activator