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S M Yu

Publications and source records attributed to S M Yu.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effects of dicentrine, a novel alpha 1-adrenoceptor antagonist, on human hyperplastic prostates.

The effects of dicentrine, an alpha 1-adrenoceptor antagonist, on human hyperplastic prostates were investigated by radioligand binding and in vitro isometric tension experiments. In human hyperplastic prostates, alpha 1-adrenoceptors were characterized by a binding assay using [3H]prazosin as a radioligand. Specific [3H]prazosin binding was saturable and of high affinity (Kd = 0.2 +/- 0.02 nM) with a maximal number of binding sites (Bmax = 55.2 +/- 3.2 fmol/mg protein). alpha-Adrenoceptor antagonists competed with [3H]prazosin for binding in the order: dicentrine > phentolamine > rauwolscine. Norepinephrine (0.3-100 microM) or phenylephrine (1-300 microM) produced gradual contractions of human hyperplastic prostates. The concentration-response curve of norepinephrine or phenylephrine was shifted in parallel to the right by dicentrine, consistent with a competitive blockade. The pA2 values of dicentrine against norepinephrine and phenylephrine were 8.04 +/- 0.09 and 8.33 +/- 0.11, respectively. These experiments were conducted to confirm that there was no interaction between alpha 1- and alpha 2-adrenoceptors in the tissue. Rauwolscine (1 microM) caused 1.7-fold, while dicentrine (0.1 microM) caused 15.8-fold shift of norepinephrine-induced contraction of human hyperplastic prostates. Combination of rauwolscine with dicentrine caused 17.8-fold shift of norepinephrine-induced prostatic tissue contraction. The contractile response to transmural field stimulation was abolished by pretreatment with tetrodotoxin, and suppressed concentration dependently by dicentrine or prazosin, whereas rauwolscine had little effect. It is concluded that dicentrine inhibits human hyperplastic prostate contractions in response to exogenous and endogenous adrenergic stimulation. Dicentrine may thus hold potential to relieve bladder outlet obstruction caused by benign prostatic hyperplasia via alpha 1-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1994

Regulation and evolution of the single alpha-tubulin gene of the ciliate Tetrahymena thermophila.

The single alpha-tubulin gene of Tetrahymena thermophila was isolated from a genomic library and shown to encode a single protein. Comparisons of the rates of evolution of this gene with other alpha-tubulin sequences revealed that it belongs to a group of more evolutionarily constrained alpha-tubulin proteins in animals, plants, and protozoans versus the group of more rapidly evolving fungal and variant animal alpha-tubulins. The single alpha-tubulin of Tetrahymena must be used in a variety of microtubule structures, and we suggest that equivalently conserved alpha-tubulins in other organisms are evolutionarily constrained because they, too, are multifunctional. Reduced constraints on fungal tubulins are consistent with their simpler microtubule systems. The animal variant alpha-tubulins may also have diverged because of fewer functional requirements or they could be examples of specialized tubulins. To analyze the role of tubulin gene expression in regulation of the complex microtubule system of Tetrahymena, alpha-tubulin mRNA amounts were examined in a number of cell states. Message levels increased in growing versus starved cells and also during early stages of conjugation. These changes were correlated with increases in transcription rates. Additionally, alpha-tubulin mRNA levels oscillate in a cell cycle dependent fashion caused by changes in both transcription and decay rates. Therefore, as in other organisms, Tetrahymena adjusts alpha-tubulin message amounts via message decay. However the complex control of alpha-tubulin mRNA during the Tetrahymena life cycle involves regulation of both decay and transcription rates.

Amino Acid Sequence↗
PubMed1994

Mechanisms of vasorelaxation induced by N-allylsecoboldine in rat thoracic aorta.

N-Allylsecoboldine was shown to be the most effective of several boldine derivatives that were tested for their vasorelaxing effect on the rat aorta. In KCl (60 mmol/l) medium, Ca2+ (0.03-3 mmol/l)-induced vasoconstriction was inhibited, concentration-dependently, by N-allylsecoboldine. The IC50 for N-allylsecoboldine was calculated to be about 4 mumol/l (for a Ca2+ concentration of 1 mmol/l). The vasorelaxant effect on KCl-induced responses was more pronounced at 60 mmol/l KCl than at 15 mmol/l KCl. Contraction of rat aorta in response to phenylephrine (0.01-100 mumol/l) was concentration-dependently inhibited by N-allylsecoboldine and by verapamil (3-30 mumol/l), while contraction in response to B-HT 920, serotonin or PGF2 alpha was not affected. This relaxing effect of N-allylsecoboldine persisted in endothelium-denuded aorta. In cultured A10 vascular smooth muscle cells, N-allylsecoboldine and verapamil displaced the binding of [3H]-prazosin (Ki values = 0.4 +/- 0.2 and 0.6 +/- 0.2 mumol/l, respectively). The increase of inositol monophosphate caused by phenylephrine in rat aorta was completely suppressed by chloroethylclonidine, but only slightly inhibited by N-allylsecoboldine and by verapamil. Glibenclamide or charybdotoxin did not affect the relaxation induced by N-allylsecoboldine of aortic rings precontracted with phenylephrine. Neither the cGMP nor the cAMP content was changed by N-allylsecoboldine. We conclude that N-allylsecoboldine relaxes the rat aorta by blocking Ca2+ channels and that it also has an antagonistic effect at alpha 1-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Pathogenesis of induced rat periapical lesions.

Studies of the mechanisms of pathogenesis of periapical lesions were undertaken using a rat model of surgical pulp exposure. In this model, periapical lesions develop rapidly between days 0 and 15 (active phase) and more slowly thereafter (chronic phase). A Gram-negative anaerobic flora, similar to that seen in human beings, are quickly established. Lesions contain a mixed inflammatory cell infiltrate consisting of T cells, neutrophils, B cells, macrophages, and plasma cells. Helper T cells predominate during the active phase, whereas suppressor T cells are more frequent in the chronic phase. Extracts of periapical lesions contain bone-resorbing activity, the highest levels of which are present when lesions are actively expanding. Most bone-resorbing activity is mediated by the cytokine interleukin-1 alpha, as determined by biochemical criteria and antibody neutralization studies. Prostaglandin2 accounts for 10% to 15% of resorptive activity. Cells that express interleukin-1 alpha were identified in pulp beginning on day 2 after exposure and in periapical tissue beginning on day 7, as determined by in situ hybridization and immunostaining. Macrophages, fibroblasts, neutrophils, and osteoclasts were positive for interleukin-1 alpha mRNA and protein. Cells that express tumor necrosis factor alpha were also detected, whereas cells expressing interleukin-1 beta or tumor necrosis factor beta were absent. Finally, periapical bone destruction was inhibited by 60% by treatment with interleukin-1 receptor antagonist. These studies establish a key role for interleukin-1 alpha in the pathogenesis of periapical lesions in the rat model.

Alveolar Bone Loss↗
PubMed1994

Expression of alpha-amylases, carbohydrate metabolism, and autophagy in cultured rice cells is coordinately regulated by sugar nutrient.

A rice suspension cell culture system has been established to study how sugar depletion regulates alpha-amylase expression, carbohydrate metabolism, and other physiological and cellular changes. It is shown here that a group of 44 kDa alpha-amylases are constitutively expressed whether or not the cells are starved of sucrose. However, expression of a new group of alpha-amylases of 46 kDa is dramatically induced when cells are starved of sucrose. Cellular sugar and starch were rapidly consumed and metabolic activity was decreased in the starved cells. Extensive autophagy also occurred in the starved cells, which caused an increase in vacuolar volume and degradation of cytoplasmic constituents including amyloplasts. Immunocytochemical studies revealed that alpha-amylases are localized in starch granules within amyloplasts, in cell walls, and in some of the vacuoles. The presence of putative signal sequences in the N-termini of nine rice alpha-amylases suggests hitherto unidentified pathways for import of alpha-amylases into amyloplasts. The studies show that differential alpha-amylase expression, carbohydrate metabolism, metabolic activity, and vacuolar autophagy are coordinately regulated by the sugar level in the medium. As the starved suspension cells exhibit some sugar-regulated characteristics of alpha-amylase expression in germinating rice embryos as well as physiological changes similar to those in senescing cells, this system represents an ideal tool for studying cellular, biochemical, and molecular biological aspects of alpha-amylase gene regulation, carbohydrate metabolism, senescence, and protein targeting in plants.

Amino Acid Sequence↗
PubMed1994

(-)-Discretamine, a selective alpha 1D-adrenoceptor antagonist, isolated from Fissistigma glaucescens.

1. The selectivity of (-)-discretamine for alpha 1-adrenoceptor subtypes was investigated by use of functional and binding studies in rat vas deferens, spleen and aorta, and in cultured DDT1MF-2 and A10 cells. 2. In prostatic portions of rat vas deferens, the competitive antagonists (-)-discretamine, 5-methylurapidil (5-MU) and prazosin inhibited contractions to noradrenaline (NA) with pA2 values of 6.21, 8.71 and 9.27, respectively. The irreversible antagonist, chloroethylclonidine (CEC, 100 microM) failed to affect contractions to NA while nifedipine (1 microM) blocked them almost completely. 3. In rat spleen, the competitive antagonists (-)-discretamine, 5-MU and prazosin inhibited contractions to phenylephrine with pA2 values of 6.44, 7.19 and 9.45, respectively. CEC (100 microM) significantly reduced the maximum contraction to phenylephrine while nifedipine (1 microM) did not affect it. 4. In rat aorta, the competitive antagonists (-)-discretamine, 5-MU and prazosin inhibited contractions to NA with pA2 values of 7.60, 8.00 and 9.40, respectively. CEC also antagonized the contractions to NA in a competitive manner with a pA2 value of 6.10. 5. The specific binding of [3H]-prazosin to DDT1MF-2 and A10 cells was concentration-dependent and saturated at 3-5 nM with KD values of 0.24 +/- 0.02 and 0.20 +/- 0.02 nM, respectively. (-)-Discretamine,5-MU, CEC and prazosin inhibited specific [3H]-prazosin binding to DDTIMF-2 and AlO cells in a concentration-dependent manner with ICso values of 390.8 +/- 20.6, 43.6 +/- 3.9, 200.0 +/- 30.0 and 0.8 +/- 0.1 nM, respectively in DDTIMF-2 cells, and 25.0 +/- 3.2, 8.6 +/- 1.4, 1000.0 +/- 30.8 and 0.52 +/- 0.03 nM, respectively in AlO cells.6. Pretreatment of Al0 cells with CEC (10 MicroM) for 30 min and then washed out thoroughly, reduced specific [3H]-prazosin binding by 30%. The CEC-insensitive [3H]-prazosin binding was inhibited by(-)-discretamine with an IC50 value of 7.0 +/- 0.3 nM.7. 5-MU (100 nM), CEC (1 MicroM) and prazosin (10 nM) markedly inhibited NA (3 MicroM)-induced [3H]-inositol monophosphate formation in DDTIMF-2 and A1O cells, while (-)-discretamine (100 nM)inhibited NA-induced [3H]-inositol monophosphate formation only in AlO cells.8. In conclusion, (-)-discretamine is a selective alpha lD-adrenoceptor antagonist in vascular smooth muscle.Its selectivity among various al-adrenoceptor subtypes is alpha 1A: alpha1B: alpha1D =0.04:0.07:1.0.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Pharmacological characterization of cinnamophilin, a novel dual inhibitor of thromboxane synthase and thromboxane A2 receptor.

1. The pharmacological effects of cinnamophilin, a new lignan, isolated from Cinnamomum philippinense, was determined in vitro in human platelet, rat isolated aorta and guinea-pig isolated trachea and in vivo in mice and guinea-pigs. 2. Cinnamophilin inhibited dose-dependently human platelet-rich plasma (PRP) aggregation induced by arachidonic acid (AA), collagen and U-46619 with IC50 of 5.0 +/- 0.4, 5.6 +/- 0.6 and 3.0 +/- 0.4 microM, respectively. The second wave of ADP- or adrenaline-induced platelet aggregation was inhibited by cinnamophilin, while the first wave was only slightly inhibited by cinnamophilin above 30 microM. 3. Cinnamophilin was found to be a thromboxane A2 (TXA2) receptor blocking agent in human platelet, rat aorta and guinea-pig trachea as revealed by its competitive antagonism of U-46619-induced aggregation of human-PRP, contraction of rat aortic rings and guinea-pig tracheal rings with pA2 values of 7.3 +/- 0.2, 6.3 +/- 0.1 and 5.2 +/- 0.2, respectively. 4. [3H]-inositol monophosphate formation and the rise of intracellular Ca2+ caused by U-46619 in human platelet was suppressed by cinnamophilin (10 microM). 5. Cinnamophilin induced a dose-dependent inhibition of thromboxane B2 (TXB2) formation, while the prostaglandin E2 (PGE2) formation was increased. Cinnamophilin did not affect unstimulated platelet adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels. When the platelets were challenged with AA, a dose-dependent rise in cyclic AMP was observed. Dazoxiben (a pure TX synthase inhibitor) and SQ 29548 (a pure TXA2 receptor antagonist) did not affect cyclic AMP levels in AA-treated platelets. 6. A high concentration of cinnamophilin (100 MicroM), failed to attenuate the contractile response of rat aorta to endothelin-l, angiotensin II, 5-hydroxytryptamine or noradrenaline. Contraction of tracheal rings induced by histamine, carbachol or KCl was also not inhibited by cinnamophilin (100 MicroM).7. Thirty min after intraperitoneal (i.p.) administration of cinnamophilin (100 microg kg-1), tail bleeding time of mice was prolonged more markedly than with indomethacin, dazoxiben or SQ 29548.8. Intravenous administration of AA (50 microg kg-1) to guinea-pig induced bronchoconstriction. Cinnamophilin(0.1 mg kg-1, i.v.) was administered 1 min before AA, the bronchoconstriction response to AA was abolished.9. It is concluded that cinnamophilin is a novel dual TX synthase inhibitor and TXA2 receptor antagonist and that it may be a useful tool for the investigation and treatment of diseases involving TXA2 disorders.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Birthweight differentials among Asian Americans.

OBJECTIVES: This study examines differentials in mean birthweight and the risk for low birthweight among various Asian-American groups in New York State (n = 499,377). METHODS: Using resident singleton live-birth records from New York State for 1985 and 1986, Asian-American births were compared with Black, American Indian, and White births. Multivariate ordinary least squares and logistic regression models were used to analyze ethnic differences. RESULTS: Compared with White births, the expected mean difference in birthweight was -115 g for Chinese, -235 g for Japanese, -164 g for Filipinos, -120 g for Blacks, and 74 g for American Indians. The risk for low birthweight was 45% higher for Filipinos and 49% higher for Blacks as compared with Whites. CONCLUSIONS: Results of this study suggest substantial heterogeneity in mean birthweight and risk for low birthweight among ethnic groups in general and the major Asian-American groups in particular. Interestingly, after controlling for ethnic differences in sociodemographic risk factors, Filipinos appear to resemble Blacks much more closely than they do their Japanese and Chinese counterparts with respect to risk for low birthweight.

Adolescent↗
PubMed1993

Effects of hyperlipidemia on the vascular reactivity in the Wistar-Kyoto and spontaneously hypertensive rats.

We studied the effects of hyperlipidemia on the vascular responsiveness in aortas isolated from control rats and rats receiving a high cholesterol-high fat (HC-HF) diet (1% cholesterol and 20% olive oil). The total plasma cholesterol, very low density lipoprotein (VLDL)-, low density lipoprotein (LDL)-cholesterol, VLDL-, LDL-, high density lipoprotein (HDL)-triglyceride levels were markedly elevated in HC-HF chow fed Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) compared to the respective normal chow fed control rats. The increase in plasma cholesterol and triglyceride levels were time-dependent. Higher levels of cholesterol and triglyceride were observed in SHR compared to WKY. In the aortic arches and abdominal aortas obtained from the SHR and WKY fed the HC-HF chow for 8 week, evoked intimal lesions were more pronounced than those noted after 4 weeks of HC-HF chow fed. The aortic arches of SHR and WKY were significantly more affected by the intimal lesion (surface area damage and fatty streak formation) than the abdominal aortas of the respective rat strain. The damage of surface area and thickness of fatty streaks were significantly augmented with the period the rats were fed the HC-HF diet. In the denuded aortic arches of the WKY and of rats receiving HC-HF diet for 8 weeks, significantly attenuated ED50 values and augmented maximal responses for phenylephrine (0.01-30 microM)-induced contraction were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Contractile effects caused by thaliporphine in the guinea-pig ileum.

The intestinal effects of thaliporphine, a potent vasoconstrictor, were studied using the isolated guinea-pig ileum. Thaliporphine (0.1-100 microM) caused contraction in a concentration-dependent manner. The contraction was not affected by pretreatment of the ileum with tetrodotoxin, phentolamine, prazosin, propranolol, naloxone, atropine, diphenhydramine, methysergide, indomethacin or staurosporine. However, the contraction was inhibited markedly by nifedipine and verapamil. These results suggest that thaliporphine causes contraction of intestinal smooth muscle by a direct effect on muscle mediated by an increased Ca2+ influx through voltage-dependent Ca2+ channels.

Animals↗
PubMed1993

Vasoconstricting effect in rat aorta caused by thaliporphine isolated from the plant Neolitsea konishii K.

Thaliporphine (0.1-100 microM) produced sustained, concentration-dependent contraction in isolated rings of rat aorta. Thaliporphine (ED50 = 1.5 +/- 0.5 microM) was less potent than endothelin (ED50 = 3.9 +/- 0.4 nM), but was more potent than Bay K 8644 (ED50 = 5.5 +/- 0.6 microM). Thaliporphine also contracted guinea-pig trachea and ileum preparations, and increased the force of beating of rat left atria, but was less potent on these tissues than on rat aorta. Thaliporphine-induced contraction of rat aorta was not affected by prazosin (0.3 microM), atropine (1 microM), saralasin (10 microM) or ketanserin (10 microM). However, the contraction was slightly potentiated by the removal of endothelium. Preincubation of the rat aorta in Ca(2+)-free Krebs solution (containing 1 mM EGTA) for 15 min completely abolished thaliporphine-induced contractions, and the subsequent addition of 3 mM CaCl2 restored thaliporphine-induced contractions to the control level. In rat aorta, thaliporphine-induced contractions were significantly reduced by nifedipine (1-30 nM) or verapamil (0.01-0.3 microM), and significantly increased by Bay K 8644 (0.1 microM) or KCl (20 mM). The pA2 values for nifedipine and verapamil against thaliporphine-induced contractions were 9.4 +/- 0.1 and 8.4 +/- 0.2, respectively. The results indicate that thaliporphine exerts its vasoconstrictor effect on rat aorta mainly by promoting Ca2+ entry.

Animals↗
PubMed1993

CIS-19, a novel platelet activating factor receptor antagonist: in vitro and in vivo studies.

The effects of CIS-19 (cis-2-(3,4-dimethoxyphenyl)-6-isopropoxy-7-methoxyl-1-(N-methylforma mido)-1,2, 3,4-tetrahydronaphthalene) was determined in vitro in rabbit platelets and in vivo in rats and guinea-pigs. CIS-19 inhibited in a selective and concentration-dependent manner the aggregation and ATP release reaction of rabbit platelets induced by PAF (4 nM). The IC50 values of CIS-19 on PAF-induced aggregation of washed platelets and platelet-rich plasma were 11.3 +/- 2.7 and 16.8 +/- 3.0 microM respectively. BN52021 also inhibited PAF-induced aggregation of washed platelets with an IC50 value of 11.7 +/- 2.8 microM. CIS-19 inhibited [3H]PAF (4 nM) binding to washed rabbit platelets with an IC50 value of 1.5 +/- 0.2 microM. The concentration-response curve of PAF-induced aggregation of washed platelets was shifted rightwards by CIS-19 with pA2 and pA10 values of 7.1 (6.8-7.3 for 95% confidence limit) and 6.1 (5.8-6.2) respectively. The thromboxane B2 formation of washed platelets caused by AA, collagen or thrombin was not affected by CIS-19 of concentrations below 400 microM. CIS-19 (25 microM) completely blocked PAF-induced, but not collagen- or thrombin-induced [3H]inositol monophosphate formation of washed platelets. When CIS-19 (2.5 and 5 mg/kg) was injected i.v. into the femoral vein, it did not affect the blood pressure of rats, but antagonized PAF (2.5 micrograms/kg, i.v.)-induced hypotensive shock either preventively or curatively. CIS-19 (2.5 and 5 mg/kg) also blocked PAF (50 ng/kg)-induced, but not AA (50 micrograms/kg)-induced, bronchoconstriction in guinea-pigs. It is concluded that CIS-19 is an effective PAF receptor antagonist not only in vitro, but also in vivo.

Adenosine Triphosphate↗
PubMed1993

Agrobacterium-mediated production of transgenic rice plants expressing a chimeric alpha-amylase promoter/beta-glucuronidase gene.

We have successfully transferred and expressed a reporter gene driven by an alpha-amylase promoter in a japonica type of rice (Oryza sativa L. cv. Tainung 62) using the Agrobacterium-mediated gene transfer system. Immature rice embryos (10-12 days after anthesis) were infected with an Agrobacterium strain carrying a plasmid containing chimeric genes of beta-glucuronidase (uidA) and neomycin phosphotransferase (nptII). Co-incubation of potato suspension culture (PSC) with the Agrobacterium inoculum significantly improved the transformation efficiency of rice. The uidA and nptII genes, which are under the control of promoters of a rice alpha-amylase gene (alpha Amy8) and Agrobacterium nopaline synthase gene (nos), respectively, were both expressed in G418-resistant calli and transgenic plants. Integration of foreign genes into the genomes of transgenic plants was confirmed by Southern blot analysis. Histochemical localization of GUS activity in one transgenic plant (R0) revealed that the rice alpha-amylase promoter functions in all cell types of the mature leaves, stems, sheaths and roots, but not in the very young leaves. This transgenic plant grew more slowly and produced less seeds than the wild-type plant, but its R1 and R2 progenies grew normally and produced as much seeds as the wild-type plant. Inheritance of foreign genes to the progenies was also confirmed by Southern blot analysis. These data demonstrate successful gene transfer and sexual inheritance of the chimeric genes.

Agrobacterium tumefaciens↗
PubMed1993

Effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity in hyperlipidaemic rats.

1. The effects of dicentrine on haemodynamic, plasma lipid, lipoprotein level and vascular reactivity were investigated in Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats, fed a high fat-high cholesterol diet. 2. In high fat-high cholesterol (HF-HC) diet fed WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) for 4 weeks caused significant reductions in total plasma cholesterol (CE) by reducing the low density lipoprotein (LDL) fraction, and reductions in total plasma triglyceride (TG) by reducing the very low density lipoprotein (VLDL) fraction. 3. Dicentrine therapy was associated with increased high density lipoprotein (HDL)-cholesterol levels; thus the ratio of total plasma cholesterol to HDL-cholesterol was improved. 4. In HF-HC diet fed conscious WKY and SH rats, oral administration of dicentrine (5 and 10 mg kg-1, twice a day) also evoked dose-related decreases in mean arterial pressure (MAP) which were of greater magnitude in SH rats. Neither dose of dicentrine caused a significant change in heart rate (HR). 5. The aortic arches from SH rats fed the HF-HC diet for 8 weeks were significantly more affected by the atherosclerotic lesions than the abdominal aortae and renal arteries of WKY and SH rats. Oral administration of dicentrine (5 and 10 mg kg-1) for 4 weeks did not diminish the atherosclerotic lesion areas in WKY and SH rats. 6. In aortae of the hyperlipidaemic rats, significantly attenuated EC50 values and augmented maximal responses for phenylephrine-induced contraction were obtained. Endothelium-dependent relaxation to acetylcholine was abolished, while endothelium-independent relaxation to nitroprusside was well preserved. Dicentrine therapy caused significantly augmented EC50 values and attenuated maximal responses for phenylephrine-induced contraction in hyperlipidaemic rats. However, dicentrine neither prevented the impaired relaxation to acetylcholine, nor affected the relaxation to nitroprusside during atherosclerosis progression.7. It is concluded that dicentrine decreases MAP, plasma CE, LDL-CE, plasma TG, VLDL-TG,vascular hyperreactivity to phenylephrine and increases HDL-CE levels. Dicentrine may thus hold potential for the reduction of two of the major risk factors, hypertension and hyperlipidaemia, for cardiovascular disease.

Animals↗
PubMed1993

Pharmacological activity of (-)-discretamine, a novel vascular alpha-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens.

1. The pharmacological activity of (-)-discretamine, isolated from Fissistigma glaucescens, was determined in rat isolated thoracic aorta, cardiac tissues and ventricular myocytes and guinea-pig isolated trachea. 2. (-)-Discretamine was found to be an alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline (pA2 = 7.20 +/- 0.10)- or phenylephrine (pA2 = 7.60 +/- 0.09)-induced vasoconstriction. It was as potent as phentolamine (pA2 = 7.51 +/- 0.10), but was more potent than yohimbine (pA2 = 6.18 +/- 0.06). Removal of endothelium significantly increased the antagonistic potency of (-)-discretamine on noradrenaline (pA2 = 7.52 +/- 0.09)- or phenylephrine (pA2 = 7.90 +/- 0.09)-induced vasoconstriction. 3. (-)-Discretamine was also an alpha 2-adrenoceptor blocking agent (pA2 = 6.30 +/- 0.15) and a 5-hydroxytryptamine antagonist (pA2 = 6.87 +/- 0.06), both in rat aorta denuded of endothelium. 4. (-)-Discretamine protected alpha-adrenoceptors from alkylation by the irreversible blocking agent, phenoxybenzamine. 5. [3H]-inositol monophosphate formation caused by noradrenaline (3 microM) in rat thoracic aorta was suppressed by (-)-discretamine (10 and 30 microM) and prazosin (3 microM). 6. A high concentration of (-)-discretamine (30 microM) did not affect the contraction induced by the thromboxane receptor agonist U-46619, prostaglandin F2 alpha (PGF2 alpha), angiotensin II, high K+ or endothelin in rat aorta denuded of endothelium. Neither cyclic AMP nor cyclic GMP content of rat thoracic aorta was changed by (-)-discretamine. 7. Contraction of guinea-pig trachea caused by histamine, leukotriene C4 or carbachol was not affected by (-)-discretamine (30 microM). (-)-Discretamine also did not block beta l- or beta2-adrenoceptor-mediated responses induced by isoprenaline in rat right atria and guinea-pig trachea.8. A voltage clamp study in rat ventricular single myocytes revealed that sodium inward current, slow inward Ca2+ current or transient (ItO) and steady state (I800) outward current was not affected by(-)-discretamine (30 microM).9. It is concluded that (-)-discretamine is a selective x-adrenoceptor and 5-HT receptor antagonist in vascular smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1992

Regulation of alpha-amylase-encoding gene expression in germinating seeds and cultured cells of rice.

Four alpha-amylase-encoding cDNA (alpha Amy-C) clones were isolated from a cDNA library derived from poly(A)+RNA of gibberellic acid (GA3)-treated rice aleurone layers. Nucleotide sequence analysis indicates that the four cDNAs were derived from different alpha Amy genes. Expression of the individual alpha Amy gene in germinating seeds and cultured suspension cells of rice was studied using gene-specific probes. In germinating seeds, expression of the alpha Amy genes is positively regulated by GA3 in a temporally coordinated but quantitatively distinct manner. In cultured suspension cells, in contrast, expression of the alpha Amy genes is negatively and differentially regulated by sugars present in the medium. In addition, one strong and one weak carbohydrate-starvation-responsive alpha Amy genes have been identified. Interactions between the promoter region (HS501) of a rice alpha Amy gene and GA3-inducible DNA binding proteins in rice aleurone cells were also studied. A DNA mobility-shift assay showed that the aleurone proteins interact with two specific DNA fragments within HS501. One fragment is located between nt -131 to -170 and contains two imperfect directly repeated pyrimidine elements and a putative GA3-response element. The other fragment is located between nt -92 to -130 that contains a putative enhancer sequence. The interactions between aleurone proteins and these two fragments are sequence-specific and GA-responsive.

Base Sequence↗
PubMed1992

Dicentrine, a novel antiplatelet agent inhibiting thromboxane formation and increasing the cyclic AMP level of rabbit platelets.

Dicentrine is an antiplatelet agent isolated from the Chinese herb Lindera megaphylla. We examined the in vitro effects of dicentrine on various aspects of platelet reactivity. Dicentrine inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA), collagen, ADP, platelet-activating factor (PAF), thrombin and U46619. Dicentrine also inhibited the thromboxane B2 formation caused by AA, collagen and thrombin in washed intact platelets or that induced by AA in lysed platelet homogenate, while prostaglandin D2 formation caused by AA was not increased. The generation of inositol monophosphates (in the presence of indomethacin) caused by thrombin, collagen and PAF was not suppressed significantly, nor did dicentrine suppress fibrinogen-induced aggregation of elastase-treated platelets. Dicentrine inhibited the intracellular Ca2+ increase in quin-2/AM-loaded platelets caused by thrombin, PAF, collagen and AA. The cyclic AMP level was elevated by dicentrine in a concentration-dependent manner. These data indicate that the inhibitory effect of dicentrine on platelet aggregation and ATP release was due to the inhibition of thromboxane formation and the elevation of the level of cyclic AMP.

Adenosine Triphosphate↗