Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether acute adaptation and resetting occur in the baroreflex control of regional vascular resistance, experiments were conducted in anesthetized and vagotomized dogs. The carotid sinuses were vascularly isolated to regulate the carotid sinus pressure (CSP) in an open-loop fashion. The hindquarters (n = 12) and mesenteric (n = 10) beds were perfused with constant flow and arterial perfusion pressures (HPP and MPP) were used to reflect changes in hindquarters and mesenteric resistance respectively. We first observed alterations in HPP and MPP during the course of CSP holding (conditioning pressure) at various levels for 15 min. Thereafter, the CSP was lowered to 50 mm Hg and increased stepwise to obtain the CSP-HPP and CSP-MPP baroreflex function curves. In experiments in the hindquarters bed, HPP stabilized at an average of 104.7 mm Hg during the initial conditioning pressure at 100 mm Hg. When conditioning pressure decreased to 50 mm Hg, the HPP increased to 125.5 mm Hg and then gradually declined to a steady level (115.6 mm Hg) in 5 min. An increase in conditioning pressure from 100 to 150 mm Hg caused HPP to decrease to 54.8 mm Hg followed by an upward adaptation to a steady level (80.2 mm Hg) in 5 min. The CSP/HPP curves constructed from the CSP step protocol were also affected by conditioning pressure. There were significant increases in the threshold and saturation pressures as conditioning pressure was elevated. However, the resetting was characterized by a parallel shift of the CSP/HPP curves without significant changes in baroreflex gain or sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute adaptation and resetting of the baroreflex control of vascular resistance in the canine hindquarters and mesentery. 841 17

Previous studies have demonstrated a deficiency in mitochondrial function in Parkinson's disease. We measured the ability of mitochondrial inhibitors of complexes I (rotenone, MPP(+), and HPP(+)), II (amdro), IV (Na cyanide), and an uncoupler (dinoseb) to release preloaded dopamine from murine striatal synaptosomes. These compounds were potent dopamine releasers, and the effect was calcium-dependent. The striatum also contains a significant density of K(ATP)(+) channels, which play a protective role during ATP decline. Blockage of these channels with glibenclamide only potentiated the dopamine release by complex I inhibitors, and a selective potentiating effect of glibenclamide on the toxicity of MPTP was also observed, in vivo, using C57BL/6 mice. Western blots of striatal dopamine transporter (DAT) and tyrosine hydroxylase (TH) proteins demonstrated that 30 mg/kg of glibenclamide alone did not affect the expression of DAT and TH after two weeks of daily treatments, but it significantly enhanced the reduction of DAT and TH by a single dose of 20 mg/kg of MPTP. Amdro or dinoseb alone, or in conjunction with glibenclamide did not alter the expression of DAT and TH. The possible mechanisms underlying dopamine release and the selectivity of glibenclamide were further evaluated, in vitro. (86)Rb efflux assay showed that glibenclamide inhibited rotenone-induced K(+) efflux, but not dinoseb-induced K(+) efflux. Analysis of ATP titers in treated synaptosomes did not support a correlation between mitochondrial inhibition and K(ATP)(+) channel activation. However, assay of reactive oxygen species (ROS) showed that greater amounts of ROS generated by complex I inhibitors was a contributory factor to K(ATP)(+) channel activation and glibenclamide potentiation. Overall, these findings suggest that co-exposure to mitochondrial complex I inhibitors and glibenclamide or a genetic defect in K(ATP)(+) channel function, may increase neurotoxicity in the striatal dopaminergic system.
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PMID:Potentiating effect of the ATP-sensitive potassium channel blocker glibenclamide on complex I inhibitor neurotoxicity in vitro and in vivo. 1672 3