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HT Syyong HHC Yang G Trinh C Cheung KH Kuo C van Breemen 《British journal of pharmacology》2009,156(4):587-600
Background and purpose:
Uridine 5''-triphosphate (UTP) is a potent vasoconstrictor of cerebral arteries and induces Ca2+ waves in vascular smooth muscle cells (VSMCs). This study aimed to determine the mechanisms underlying UTP-induced Ca2+ waves in VSMCs of the rat basilar artery.Experimental approach:
Isometric force and intracellular Ca2+ ([Ca2+]i) were measured in endothelium-denuded rat basilar artery using wire myography and confocal microscopy respectively.Key results:
Uridine 5''-triphosphate (0.1–1000 µmol·L−1) concentration-dependently induced tonic contraction (pEC50 = 4.34 ± 0.13), associated with sustained repetitive oscillations in [Ca2+]i propagating along the length of the VSMCs as asynchronized Ca2+ waves. Inhibition of Ca2+ reuptake in sarcoplasmic reticulum (SR) by cyclopiazonic acid abolished the Ca2+ waves and resulted in a dramatic drop in tonic contraction. Nifedipine reduced the frequency of Ca2+ waves by 40% and tonic contraction by 52%, and the nifedipine-insensitive component was abolished by SKF-96365, an inhibitor of receptor- and store-operated channels, and KB-R7943, an inhibitor of reverse-mode Na+/Ca2+ exchange. Ongoing Ca2+ waves and tonic contraction were also abolished after blockade of inositol-1,4,5-triphosphate-sensitive receptors by 2-aminoethoxydiphenylborate, but not by high concentrations of ryanodine or tetracaine. However, depletion of ryanodine-sensitive SR Ca2+ stores prior to UTP stimulation prevented Ca2+ waves.Conclusions and implications:
Uridine 5''-triphosphate-induced Ca2+ waves may underlie tonic contraction and appear to be produced by repetitive cycles of regenerative Ca2+ release from the SR through inositol-1,4,5-triphosphate-sensitive receptors. Maintenance of Ca2+ waves requires SR Ca2+ reuptake from Ca2+ entry across the plasma membrane via L-type Ca2+ channels, receptor- and store-operated channels, and reverse-mode Na+/Ca2+ exchange. 相似文献997.
998.
BACKGROUND: The mechanism by which hypertriglyceridemia (HTG) leads to pancreatitis is not clear. We sought to determine whether the genes involved in pancreatic ductal or acinar cell injury, including the cationic trypsinogen gene [protease, serine, 1 (trypsin 1) (PRSS1)], the pancreatic secretory trypsin inhibitor gene [serine peptidase inhibitor, Kazal type 1 (SPINK1)], the cystic fibrosis transmembrane conductance regulator gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette subfamily C, member 7) (CFTR)], and inflammation genes such as tumor necrosis factor [tumor necrosis factor, TNF superfamily, member 2 (TNF)] are associated with hyperlipidemic pancreatitis (HLP) in patients with HTG. METHODS: We performed genetic analysis of 126 HTG patients in Taiwan (46 with HLP and 80 without HLP). The entire coding and intronic regions of the PRSS1, SPINK1, and CFTR genes were identified by heteroduplex analysis techniques and were confirmed by sequencing analysis. The presence of 125G/C, 1001 + 11C>T, 1540A>G (Met470Val), 2694T>G, and 4521G>A in CFTR, the presence of 272C>T in SPINK1, and TNF promoter polymorphisms (nucleotide positions 1031, 863, 857, 308, and 308) were measured by direct sequencing. RESULTS: Of the 126 HTG patients, 13 (10.3%) carried a CFTR mutation. No PRSS1 or SPINK1 mutations were detected in our patients or in HTG controls. The CFTR gene mutation rates in HTG with and without HLP were 26.1% (12 of 46) and 1.3% (1 of 80), respectively (P <0.0001). The CFTR gene mutations were all Ile556Val. A multivariate analysis of HTG patients indicated that triglycerides, CFTR 470Val, and TNF promoter 863A were independent risk markers for HLP. CONCLUSIONS: This genetic study is the first one to address the association of HLP with the CFTR mutation/variant/haplotype and TNF promoter polymorphism in a Chinese HTG population. The results suggest that the occurrence of HLP is multifactorial and polygenic. 相似文献
999.
Campbell LA Kuo CC Suchland RJ Rothstein DM 《Antimicrobial agents and chemotherapy》2008,52(5):1855-1858
The efficacy of rifalazil and other benzoxazinorifamycins was tested in a mouse model of lung infection against Chlamydia pneumoniae. Rifalazil and six related new chemical entities all showed efficacy after one dose per day for 3 days at either 3 or 1 mg/kg of body weight. 相似文献
1000.
We compared the symptoms of 91 Taiwanese women, 50 pregnant by assisted reproductive technology (ART), with those of 41 women, pregnant without assistance. They completed a self-administered demographic questionnaire and symptomatology inventory (SI) during each trimester. The ART group had a higher frequency of complications and hospitalizations than the unassisted women. No significant differences were found in physical and affective symptoms in the ART group across three trimesters, but significant differences were found in the unassisted group. In addition, ART and non-ART women differed in types of individual symptoms experienced each trimester. These findings suggest the need for nurses to assess each group for the presence of specific symptoms throughout pregnancy and to provide individualized symptom management. 相似文献