Zhongguo yao li xue bao = Acta pharmacologica Sinica最新文献

Aim: To study the suppressive effect of flutamide (Flu) on benign prostate hypertrophy.

Methods: The effect of Flu 10, 25, and 50 mg.kg-1 i.g. on the prostate was tested in orchiectomized rats with s.c. testosterone daily for 30 d and in mice implanted with homologous strain fetal mouse urogenital sinus for 14 d.

Results: 1) Flu dose-dependently suppressed the weight and volume of each lobe of the prostate to about 10%-50% of control. Also, the acini and height of epithelial cells atrophied. The effect was more powerful than that of estradiol (Est). 2) The weight and volume of the mouse prostate diminished in Flu-treated groups, but the dose-response relationship was seen only in volume. In this model, Est was better than Flu.

Conclusion: Flu possesses the suppressive action on benign prostate hypertrophy.

Aim: To characterize the internalization of delta opioid receptors (DOR) stably expressed in Chinese hamster ovary (CHO) cells and the role of the C-terminal in this process.

Methods: Receptor membrane anchoring was shown by immunofluorescence microscopy. Receptor internalization was assessed by measuring the radioligand binding resistant to the acid-buffer wash.

Results: Originally, all the wild-type (CHO-W) and C-truncated (CHO-T) DOR expressed were localized to the membrane. Agonist [3H] leucine-2-alanine enkephalin (LAE) but not the antagonist [3H]diprenorphine (Dip) induced rapid receptor internalization. The internalization of C-truncated DOR in CHO-T was similar to that of the wild-type in maximal level, but climbed up more slowly. DOR internalization was extracellular osmolarity- and temperature-sensitive. Pertussis toxin and universal protein kinase inhibitor staurosporine had no effect on it.

Conclusion: DOR internalization is an agonist and clathrin-coated pits dependent, but post-receptor cellular signal transduction independent process; moreover, the C-terminal of DOR, not engaged in membrane anchoring, affects the initialization of DOR internalization.

Aim: To study the effect of dauricine on CsCl-induced early afterdepolarizations (EAD) and ventricular arrhythmias in rabbits.

Methods: Monophasic action potentials (MAP) of the left ventricle of the rabbit heart in situ were recorded with MAP recording technique. CsCl 1-2 mmol.kg-1 i.v. was used to induce EAD and ventricular arrhythmias.

Results: CsCl resulted in decrease of MAP amplitude (MAPA, P < 0.05) and prolongation of MAP duration at 90% repolarization (MAPD90, P < 0.01), QRS, and R-R duration (P < 0.05) compared with those before CsCl in the dauricine and control group. CsCl injection induced EAD that appeared within about 30 s and disappeared 5-15 min thereafter. EAD always preceded ventricular arrhythmias including ventricular premature beats and paroxysmal ventricular tachycardia. The EAD amplitude (EADA) in the dauricine group (26% +/- 9% of MAPA) was smaller than that in the control group (52% +/- 5% of MAPA, P < 0.05) and the incidence of arrhythmias in dauricine group (28%) was lower than that in control group (80%, P < 0.05).

Conclusion: Dauricine exerted an antagonistic effect on EAD and suppressed triggered ventricular arrhythmias by decreasing EADA.

Aim: To study the possibility of dauricine (Dau) inhibiting redistribution of platelet membrane glycoprotein IV (GPIV) and release of intracellular alpha-granule thrombospondin (TSP) on platelet activation.

Methods: Using the flow cytometric assay of washed platelet to record expression of GPIV and release of TSP induced by thrombin.

Results: Dau did not affect GPIV and TSP on resting platelet membrane but inhibited redistribution of GPIV to the platelet surface and TSP release on activated platelet. There was a marked positive correlation between changes of GPIV and TSP (r = 0.511, P < 0.01). The inhibitory effect of Dau appeared not to be Ca2+ concentration-dependent.

Conclusion: Dau inhibited redistribution of GPIV and release of intracellular alpha-granule thrombospondin induced by thrombin.

Aim: To compare the efficacy and safety between huperzine-A (Hup) in capsules and tablets for treating patients with Alzheimer disease (AD).

Methods: Using multicenter, prospective, double-blind, double-mimic, parallel, positive controlled and randomized methods, 60 patients meeting with the NINCDS-ARDRA criteria of AD were divided into 2 equal groups. Patients in the capsule group received 4 capsules of Hup (each contains 50 micrograms) and 4 tablets of placebo (lactose and starch inside); while the tablet group received 4 tablets of Hup (each contains 50 micrograms) and 4 capsules of placebo, p.o., twice a day for 60 d. All the patients were evaluated with a lot of related ranting scales, and physiological and laboratory examination.

Results: There were significant differences (P < 0.01) on all the psychological evaluations between 'before' and 'after' the 60-d trial of 2 groups, but there was no significant difference between 2 groups by group t test (P > 0.05). The changes of oxygen free radicals in 2 groups showed marked improvement. No severe side effect besides moderate to mild nausea was found in both groups.

Conclusion: There is equal efficacy and safety between Hup in capsule and tablet for treating patients with AD, and Hup can reduce the pathological changes of the oxygen free radicals in the plasma and erythrocytes of patients with AD.

Aim: To study the anti-inflammatory effects of total saponins of Panax notoginseng (PnS).

Methods: Rat air-pouch acute inflammatory model was established with s.c. carrageenan (Car, 25 mg.kg-1). The protein content in exudate was measured. Micro-acid titration assay and radioimmunoassay (RIA) were applied respectively to investigate effects of PnS on phospholipase A2 (PLA2) activity and dinoprostone (Din) content in exudate. Fura-2 fluorescence technique was used to determine the intracellular free calcium concentration in neutrophils (Neu-[Ca2+]i).

Results: At 12 h, PnS 60-240 mg.kg-1 i.p. reduced Neu counts, protein content [(7.7 +/- 1.3) to (4.4 +/- 1.4) g.L-1], and Din content [(1619 +/- 391) to (883 +/- 268) ng.L-1]; inhibited the PLA2 activity in exudate [(248 +/- 42) to (157 +/- 35) kU.L-1] in a dose-dependent manner. PnS 60, 120, and 240 mg.kg-1 lowered the level of Neu-[Ca2+]i with the inhibitory rate of 9.1%, 33.2%, and 39.4%, respectively.

Conclusion: PnS has an obvious anti-inflammatory effect and its mechanisms are related to the inhibition of the Neu-[Ca2+]i level and PLA2 activity, and reduction of Din content.

Aim: To study the mechanism of antidiuretic effect of suberogorgin (Sub).

Methods: Conscious rat was given i.g. Sub 3.16 mg.kg-1 20 min after water-loaded treatment and then urine was collected in metabolic cage. Ion excretion was determined in atomic emission spectrometry. Urinary prostaglandin E (PGE), plasma PGE, antidiuretic hormone (ADH), and aldosterone were measured with RIA. Sub vs pituitrin or DOCA effects were carried out in hypophysectomized or adrenalectomized rats.

Results: The urine volume and the excretions of urinary sodium and potassium were decreased, maximally by 91%, 76%, and 86%, during the 24-h period after Sub. This antidiuretic effect possessed a progressive weakening with time. The concentrations of urinary PGE, plasma PGE, and ADH were increased by 25%, 212%, and 538%, respectively, but plasma aldosterone was not significantly influenced, 2 h after Sub dosing. The response of urine-excretion of rat to Sub was almost resisted by hypophysectomy but not by adrenalectomy.

Conclusion: Sub decreased the urine excretion by, at least in part, accelerating the secretion of ADH but neither by PGE nor by aldosterone.

Aim: To study the effect of aerobic exercise and its combination with Gin (ginsenosides from stems and leaves of ginseng) on lipid metabolism in diet-induced hyperlipidemia mice.

Methods: The mouse hyperlipidemia model was set up by feeding high cholesterol diet. Unloaded swimming was designed to be a manner of aerobic exercise. The effects of aerobic exercise and its combination with Gin on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-c) in serum, malondialdehyde (MDA), and superoxide dismutase (SOD) in liver tissue were measured; the thymus and liver were weighed.

Results: (1) The mouse hyperlipidemia model was set up successfully: TC and MDA increased (P < 0.05) but HDL-c and SOD decreased (P < 0.05); the liver weight increased and the thymus weight reduced; fatty liver was found; (2) aerobic exercise reduced TC but increased MDA and HDL-c in cholesterol-rich diet mice; the liver weight did not reduce, and fatty liver did not clear up; and (3) when aerobic exercise combined with Gin, TC and TG decreased markedly (P < 0.01), and MDA also decreased (P < 0.05); SOD and HDL-c increased markedly (P < 0.01); the thymus weight increased and the liver weight decreased to normal level; fatty liver cleared up.

Conclusion: Aerobic exercise could lower serum lipid to some extent but could not satisfactorily regulate lipid metabolism. When combined with Gin, aerobic exercise could better lower serum lipid, regulate lipid metabolism, promote antioxidation, and enhance immune activity.

Aim: To study the early changes of cardiac angiotensin (Ang) II receptor gene transcription after myocardial infarction (MI) in rats chronically treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril.

Methods: MI was induced by left anterior descending coronary artery ligation in rats and sham-operated rats were used as control. Rats were treated daily with ramipril (1 mg.kg-1) or water, initiated 1 wk before surgery. Quantitative RT-PCR was applied to determine the Ang II receptors AT1, AT2 receptor gene mRNA levels in the non-infarcted myocardium.

Results: AT1 and AT2 mRNA levels increased time point-dependently in the cardiac septum after MI reaching a peak on d 1. There was no significant difference of the myocardial AT1 and AT2 receptor mRNA levels between the ramipril-treated and water-treated rats after MI.

Conclusion: The AT1 and AT2 receptor gene transcription in the non-infarcted myocardium was associated with the process of cardiac remodeling after MI but not affected by ACE inhibition.

Aim: To study the effects of several 5-hydroxytryptamine (5-HT) receptor subtype antagonists on 5-HT-induced depolarization and the effects of 5-HT1P receptor agonist on the membrane potential in the neurons of guinea pig inferior mesenteric ganglion (IMG).

Methods: Intracellular recordings were made from neurons of the isolated guinea pig IMG.

Results: Cyproheptadine (5-HT1/2 antagonist 10 mumol.L-1, n = 7) and BRL 24924 (5-HT1P antagonist 10 mumol.L-1, n = 19) reversibly suppressed 5-HT slow response; pressure ejection of MCPP (5-HT1P agonist 10 mmol.L-1) induced a slow depolarization in most of 5-HT sensitive neurons (10/14).

Conclusion: 5-HT-induced slow depolarization is mediated by 5-HT1P receptor.