The formation of the pyrrolic alcohol glutathione (GSH) conjugates of two different types of pyrrolizidine alkaloids (PAs), i.e. clivorine (an otonecine-type PA) and retrorsine (a retronecine-type PA), was investigated with rat microsomes in the presence of GSH. Two GSH conjugates identified as metabolites of retrorsine were the pyrrolic alcohol conjugated with one [7-GSH-dehydroretronecine (DH...

In this study, we measured the activity of dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase (DHP) and beta-ureidopropionase (beta-UP), using radiolabeled substrates, in 16 different tissues obtained at autopsy from a single patient. The activity of DPD could be detected in all tissues examined, with the highest activity being present in spleen and liver. Surprisingly, the highest acti...

DA-1131, a new carbapenem antibiotic, undergoes renal metabolism by renal dehydropeptidase I (DHP-I), located on the brush border of the proximal tubular cell. Species differences with regard to the effects of cilastatin, a renal DHP-I inhibitor, were investigated after a 1-min intravenous infusion of DA-1131, with or without cilastatin, to rats, rabbits, and dogs. After intravenous infusion, t...

Investigators from the University of California, Los Angeles (UCLA), and members of the leadership and data analysis teams at UnitedHealthcare (UHC) are partnering to evaluate the Diabetes Health Plan (DHP), an innovative disease-specific insurance product designed by UHC specifically for patients with prediabetes or diabetes. The DHP provides improved access to care management, telephone coach...

Dehaloperoxidase (DHP) from the annelid Amphitrite ornata is a catalytically active hemoglobin-peroxidase that possesses a unique internal binding cavity in the distal pocket above the heme. The previously published crystal structure of DHP shows 4-iodophenol bound internally. This led to the proposal that the internal binding site is the active site for phenol oxidation. However, the native su...

Adrenergic, cholinergic, and a variety of peptide neurotransmitters are known to modulate Ca currents in peripheral neurons. Using a protocol that allows for simultaneous assessment of effects on dihydropyridine (DHP)-sensitive and DHP-insensitive current components, we compared the actions of norepinephrine (NE), bethanechol (BeCh), and neuropeptide Y (NPY) on Ca currents in neonatal rat super...

The role of calcium as an activator and regulator of many biological processes is linked to the ability of the cell to rapidly change its cytoplasmic calcium levels. Calcium acts as an intracellular messenger in hormone-induced bud formation during the development of the moss Physcomitrella patens. Calcium transport and ligand binding studies have implicated plasma membrane-localized 1, 4-dihyd...

To elucidate the mechanism underlying the interaction between the L-type Ca2+ channel and the dihydropyridines (DHPs), contribution of the repeat III was studied by constructing chimeras between the DHP-sensitive alpha1C and DHP-insensitive alpha1E subunits. The chimeras were transiently expressed in human embryonic kidney 293 cells and the whole-cell Ba2+ current (IBa) was recorded. Mutating T...

An endocrine-disrupting chemical, diethylstilbestrol (DES), a nonsteroidal estrogen, triggers oocyte maturation in fish. The morphology (the time course of the change in germinal vesicle breakdown) and an intracellular molecular event (the de novo synthesis of cyclin B) induced by DES were indistinguishable from those induced by a natural maturation-inducing hormone, 17alpha,20beta-dihydroxy-4-...

Direct hemoperfusion therapy with polymyxin B immobilized fiber cartridge (PMX-DHP) is an established strategy in the treatment of septic shock in Japan and parts of Western Europe. PMX-DHP is currently the subject of a pivotal North American randomized controlled trial (EUPHRATES) in patients with septic shock and confirmed endotoxemia, as measured by the endotoxin activity assay. The major me...