General pharmacology
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General pharmacology · Oct 2000
Quantification of pulmonary capillary endothelium-bound angiotensin converting enzyme inhibition in man.
Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme expressed abundantly on the pulmonary capillary endothelium and recognized as the site for the conversion of circulating angiotensin I to II. In the present study, we have applied recently developed methodologies for assaying pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately blood was withdrawn from a radial arterial catheter. ⋯ This treatment had no significant effect on mean arterial pressure (91+/- 6 vs. 84 +/- 7 vs. 88 +/- 6 mm Hg for T(0), T(15) and T(120), respectively), but significantly decreased serum and PCEB ACE activities. When normalized to predrug (T(0)) activity levels, enalaprilat inhibited PCEB and serum ACE activities at T(15) 74 +/- 6% and 68 +/- 6%, respectively. However, 2 h after enalaprilat (T(120)), PCEB ACE inhibition was maintained at 66 +/- 7%, whereas serum ACE inhibition was reduced to 46 +/- 8% (P<.01 from PCEB ACE), suggesting a preferential PCEB ACE inhibitory effect of enalaprilat.
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General pharmacology · May 2000
Activation of caspase cascades in Korean mistletoe (Viscum album var. coloratum) lectin-II-induced apoptosis of human myeloleukemic U937 cells.
Mistletoe lectins are of high biological activity and exert cytotoxic effects. We have previously shown that Korean mistletoe, Viscum album var. coloratum, lectin-II specifically induces apoptotic cell death in cancer cells, not normal lymphocytes. The destructive mechanism by mistletoe lectins on tumor cells was mediated by activation of c-JUN N-terminal kinase (JNK)/stress-activated protein kinase. ⋯ Consistent with catalytic activation of protease, both poly(ADP-ribose) polymerase (PARP) and protein kinase C-delta (PKC-delta) are also cleaved in mistletoe lectin-II-treated U937 cells. An inhibitor of caspase-3-like protease, DEVD-CHO peptide, significantly inhibited mistletoe lectin-II-induced apoptosis, PARP cleavage, and fragmentation of DNA. These results provide the evidence that Korean mistletoe lectin-II induces apoptotic death of U937 cells via activation of caspase cascades.
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General pharmacology · Oct 1999
Cardiac effects of non-depolarizing neuromuscular blocking agents pancuronium,vecuronium, and rocuronium in isolated rat atria.
Pancuronium, vecuronium, and rocuronium produce different cardiac effects. Using spontaneously beating right and electrically stimulated left rat atria, while measuring developed force, effective refractory period, and heart rate, we determined and compared the concentration-dependent cardiac effects of the compounds. ⋯ These effects may be the result of a blockade of the M2 muscarinic receptors. However, the concentrations required to produce changes were higher than those observed in patients under neuromuscular blockade.
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Ginsenoside Rc, Rd, and Re induced antinociception in writhing and formalin tests among five representative ginsenosides: Rb1, Rc, Rd, Re, and Rg1. However, these ginsenosides had no effect in the tail-flick test. The antinociceptive effects induced by three ginsenosides were dose dependent. ⋯ These three ginsenosides did not affect motor function. Ginsenoside Rc and Rd induced hypothermia for 30 to 60 min, and ginsenoside Rc induced hyperthemia after 150 min of treatment at doses of 100 mg/kg. These results suggest that ginsenosides such as Rc, Rd, or Re inhibit mainly chemogenic pain rather than thermal pain by the nonopioid system in mice.
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General pharmacology · Sep 1998
Calcium release by diltiazem from isolated sarcoplasmic reticulum of rabbit skeletal muscle.
1. The effect of diltiazem on isolated sarcoplasmic reticulum (SR) from rabbit skeletal muscle was studied. To observe calcium movement into and out of the SR, a fluorescent chelate probe technique with chlortetracycline (CTC) as a reagent was employed. 2. ⋯ Addition of EGTA to the media chelates external calcium and caused calcium release that can be reversed by further addition of calcium chloride. Similarly diltiazem caused a rapid release of accumulated calcium from the SR, which is not reversed by the addition of calcium chloride. 5. It seems that the effect of diltiazem may be related to SR membrane-bound calcium being available for release.