T he classical paradigm of steroid hormone action is that intracellular receptors bind to specific steroids to modulate gene expression within the nuclei of target cells. However, increasing evidence now suggests that many important steroidinduced signaling events are triggered independent of transcription. Examples of ‘‘nongenomic’’ biological responses to steroids include estrogen-induced pro...

The effects of N-monomethyl-L-arginine (L-NMMA), a nitricoxide synthase (NOS) inhibitor, on the L-type Ca current (ICa) and NO effects on NOS were determined in rat ventricular myocytes. L-NMMA (10 and 100 mM) had no significant effect on basal ICa, but in a cAMP-stimulated condition due to forskolin (1 mM) or milrinone (10 mM), a cGMP-inhibited cAMPphosphodiesterase (PDE), L-NMMA (10 and 100 m...

The present study underlines the importance of gemfibrozil, a lipid-lowering drug and an activator of peroxisome proliferatoractivated receptor(PPAR), in inhibiting the disease process of adoptively transferred experimental allergic encephalomyelitis (EAE), an animal model of relapsing-remitting multiple sclerosis. Clinical symptoms of EAE, infiltration of mononuclear cells, and demyelination w...

Administration of selective and nonselective cyclooxygenase (COX)-2 inhibitors to rheumatoid arthritis patients taking low doses of acetylsalicylic acid (ASA) for cardiovascular prevention associates with increased risk of gastrointestinal bleeding. The present study was undertaken to investigate whether administration of HCT-3012 [(S)-6-methoxy-methyl-2-naphthaleneacetic acid 4-(nitrooxy)butyl...

The ATP-driven drug efflux pump, P-glycoprotein, is a critical and selective element of the blood-brain barrier and a primary impediment to pharmacotherapy of central nervous system (CNS) disorders. Thus, an understanding of how P-glycoprotein function is regulated has the potential to improve CNS therapy. We recently demonstrated rapid (minutes) and reversible inactivation of P-glycoprotein in...

( )-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide] (NOR-3), a nitric-oxide (NO) donor, is known to increase HCO3 secretion in rat stomachs, intracellularly mediated by cGMP; yet, there is no information about the phosphodiesterase (PDE) isozyme involved in this process. We examined the effects of various isozyme-selective PDE inhibitors on the secretion of HCO3 in the mouse stomach in v...

Demonstration that I B kinase 2 (IKK-2) plays a pivotal role in the nuclear factorB-regulated production of proinflammatory molecules by stimuli such as tumor necrosis factor (TNF)and interleukin (IL)-1 suggests that inhibition of IKK-2 may be beneficial in the treatment of rheumatoid arthritis. In the present study, we demonstrate that a novel, potent (IC50 17.9 nM), and selective inhibitor of...

The mortality rate for septic patients with acute renal failure is approximately doubled compared with patients with sepsis alone. Unfortunately, the treatment for sepsis-induced renal failure has advanced little during the last several decades. Because sepsis is often caused by lipopolysaccharide (LPS), a mouse model of LPS challenge was used to study the development of kidney injury. We hypot...

Grapeseed Proanthocyanidin [GSP] seeds possessing a potent antioxidant and cardioprotective properties were evaluated against Doxorubicin induced cardiotoxicity in rats. Intraperitonial injection of DOX [10mg kgˉ1 /b.wt] administrated once a day for 15 days was revealed by elevated serum creatine phoshokinase [CPK] lactatedehydrogenase [LDH] aspartate transaminase [ASP] alanine transaminase [AL...