Tyrosine kinase inhibitor, genistein, inhibits macroscopic L-type calcium current in rat portal vein smooth muscle cells

1997 ◽  
Vol 75 (9) ◽  
pp. 1058-1062 ◽  
Author(s):  
H Liu ◽  
K Li ◽  
N Sperelakis
Keyword(s):  
Smooth Muscle ◽  
Portal Vein ◽  
Tyrosine Kinase ◽  
Smooth Muscle Cells ◽  
Tyrosine Kinase Inhibitor ◽  
Calcium Current ◽  
Kinase Inhibitor ◽  
Muscle Cells ◽  
Rat Portal Vein

Tyrosine kinase inhibitors suppress endotoxin- and IL-1 beta-induced NO synthesis in aortic smooth muscle cells

1993 ◽  
Vol 265 (3) ◽  
pp. H1014-H1018 ◽  
Author(s):  
N. Marczin ◽  
A. Papapetropoulos ◽  
J. D. Catravas
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Kinase ◽  
Smooth Muscle Cells ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

Nitric oxide (NO) formation via the expression of an endotoxin- and cytokine-inducible NO synthase (iNOS) within the vascular smooth muscle is thought to be responsible for the cardiovascular collapse that occurs during septic shock and antitumor therapy with cytokines. Because the molecular mechanisms that underlie induction of iNOS are still unclear and because tyrosine kinases are implicated in interleukin-1 beta (IL-1 beta)-induced prostaglandin synthesis in mesangial cells and in NO generation by an insulinoma cell line, we investigated the influence of tyrosine kinase inhibitors on iNOS induction in cultured rat aortic smooth muscle cells (RASMC). The production of biologically active NO was demonstrated by L-arginine-dependent guanosine 3',5'-cyclic monophosphate (cGMP) accumulation after a 3-h exposure to either IL-1 beta or lipopolysaccharide (LPS). Pretreatment of RASMC for 30 min with the tyrosine kinase inhibitor genistein prevented both IL-1 beta- and LPS-elicited cGMP accumulation in a concentration-dependent manner. Geldanamycin, a chemically different tyrosine kinase inhibitor, also blocked cGMP formation in response to both LPS and IL-1 beta at nanomolar concentrations. Genistein and geldanamycin inhibited cGMP accumulation even when added 90 min after LPS exposure, but no inhibition was observed when they were included at later time points (120-180 min), suggesting that the inhibitors had no direct effect on iNOS activity after its induction. Formation of cGMP in response to sodium nitroprusside and to NO released from bovine aortic endothelial cells remained virtually unaffected by genistein and geldanamycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document