Biomedical subjects

F N Ko

Publications and source records attributed to F N Ko.

At least 73 records · Page 4Linked to original sources

PubMed1995

Characterization of alpha 1-adrenoceptor subtypes in tension response of human prostate to electrical field stimulation.

1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical field stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked these effects by only 50%. 3. The contractile responses of rat vas deferens and spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha 1A-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical field stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 microM), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5. The involvement of prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined. Clonidine (3 x 10-9 to 3 x 10- M) blocked concentration-dependently the contractile response to electrical field stimulation of human prostate and this inhibitory effect was reversed by yohimbine (10-7 M). Additionally, the inhibitory effect of CEC (3 x 10-6 to 3 x 10-4 M)to the nerve-mediated contraction was also partially reversed by yohimbine (10-7 M).6. It is suggested that the putative czA-adrenoceptors in human prostate may be functionally confined to the synaptic region whereas only minor populations of the putative alpha 1B- and/or alpha 1c-adrenoceptors exist in this region.

Adrenergic Antagonists↗

PubMed1995

YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase.

1. Our previous study demonstrated that YC-1, a derivative of benzylindazole, is a novel activator of soluble guanylate cyclase (sGC) in rabbit platelets. This work investigated whether the antiplatelet effect of YC-1 was mediated by a nitric oxide (NO)/sGC/cyclic GMP pathway in human platelets. 2. In human washed platelets, YC-1 inhibited platelet aggregation and ATP released induced by U46619 (2 microM), collagen (10 micro ml(-1)) and thrombin (0.1 u ml(-1)) in a concentration-dependent manner with IC50 values of (microM) 2.1 +/- 0.03, 11.7 +/- 2.1 and 59.3 +/- 7.1, respectively. 3. In a 30,000 g supernatant fraction from human platelet homogenate, YC-1 (5-100 microM) increased sGC activity in a concentration-dependent manner. At the same concentration-range, YC-1 elevated cyclic GMP levels markedly, but only slightly elevated cyclic AMP levels in the intact platelets. 4. MY-5445, a selective inhibitor of cyclic GMP phosphodiesterase, potentiated the increases in cyclic GMP caused by YC-1, and shifted the concentration-anti-aggregation curve of YC-1 to the left. In contrast, HL-725, a selective inhibitor of cyclic AMP phosphodiesterase, did not affect either the increases in cyclic nucleotides or the anti-aggregatory effect caused by YC-1. 5. Methylene blue, an inhibitor of sGC, blocked the increases of cyclic GMP caused by YC-1, and attenuated markedly the anti-aggregatory effect of YC-1. The adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA) did not affect YC-1-induced inhibition of platelet aggregation. 6. Haemoglobin, which binds NO, prevented the activation of sGC and anti-aggregatory effect caused by sodium nitroprusside, but did not affect YC-1 response. 7. These results would suggest that YC-1 activates sGC of human platelets by a NO-dependent mechanism, and exerts its antiplatelet effects through the sGC/cyclic GMP pathway.

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

PubMed1995

Characterization of the thromboxane (TP-) receptor subtype involved in proliferation in cultured vascular smooth muscle cells of rat.

1. The effects of the thromboxane A2 (TxA2)-mimetic, U-46619, on the proliferation of vascular smooth muscle cells (VSMCs) were examined in a clonal smooth muscle cell line, A10, which was derived from foetal rat aorta. 2. [3H]-U-46619 bound to A10 cells of passages 18-20 (p18-20) with two classes of sites. The high affinity site showed a Bmax of 3.0 +/- 1.8 fmol mg-1 protein with a KD value 1.0 +/- 0.1 nM, while the low affinity site showed a Bmax of 43.0 +/- 6.0 fmol mg-1 protein and KD value of 129.0 +/- 7.9 nM. However, [3H]-U-46619 bound to A10 cells from passages 28-30 (p28-30) at a single class of site with a Bmax 111.0 +/- 9.0 fmol mg-1 protein and a KD value of 175.4 +/- 22.0 nM. 3. Cinnamophilin and SQ29548 inhibited specific [3H]-U-46619 binding to p18-20 A10 cells in a concentration-dependent manner with Ki values of 390.0 +/- 3.2 and 4.6 +/- 1.0 nM, respectively at a high affinity site, and 2.6 +/- 0.2 microM and 310.0 +/- 6.4 nM, respectively at the low affinity site. 4. U-46619 produced isometric contractions of rat aorta in a concentration-dependent manner with an EC50 7.0 +/- 1.2 nM. Cinnamophilin and SQ29548 antagonized U-46619-induced aortic contractions with pA2 values 6.3 +/- 0.1 and 8.2 +/- 0.2, respectively. 5. U-46619 increased [3H]-thymidine incorporation into DNA of p18-20 and p28-30 A10 cells in aconcentration-dependent manner with EC50 values 362.7 +/- 27.0 and 302.5 +/- 20.1 nm, respectively. The U-46619-induced increase of [3H]-thymidine incorporation into DNA of p28 -30 AO0 cells was potentiatedby PDGF (1 ng ml-1) and FCS (1%) and was inhibited by cinnamophilin (10 microM) and SQ29548 (1 microM)with estimated pKB values 5.4 +/- 1.2 and 6.3 +/- 0.9, respectively.6. Cell cycle analysis revealed that U-46619-increased cell cycle progression was primarily due to a rapidtransition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, U-46619 also increasedprotein synthesis and cell numbers in VSMC. All these effects of U-46619 were inhibited bycinnamophilin and SQ29548.7. U-46619 caused phosphoinositide breakdown and increased the intracellular Ca2+ concentration inVSMC, effects which were blocked by cinnamophilin and SQ29548.8 These data indicate there are two U-46619 binding sites in AlO VSMC. The high affinity site is correlated to U-46619-induced vasoconstriction while the low affinity site is correlated to U-46619-mediated VSMC proliferation. These data also reveal that U-46619 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. Since cinnamophilin inhibits TPreceptor-mediated VSMC proliferation, it may thus hold promising potential for the prevention of atherosclerosis or vascular diseases.

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

PubMed1995

Antiplatelet effect of gingerol isolated from Zingiber officinale.

The purpose of this investigation was to determine the antiplatelet mechanism of gingerol. Gingerol concentration-dependently (0.5-20 microM) inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 (9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha) and thrombin. Gingerol also concentration-dependently (0.5-10 microM) inhibited thromboxane B2 and prostaglandin D2 formation caused by arachidonic acid, and completely abolished phosphoinositide breakdown induced by arachidonic acid but had no effect on that of collagen, PAF or thrombin even at concentrations as high as 300 microM. In human platelet-rich plasma, gingerol and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate (ADP, 5 microM) and adrenaline (5 microM) but had no influence on the primary aggregation. The maximal antiplatelet effect was obtained when platelets were incubated with gingerol for 30 min and this inhibition was reversible. It is concluded that the antiplatelet action of gingerol is mainly due to the inhibition of thromboxane formation.

Adenosine Triphosphate↗

PubMed1995

Synthesis and antiplatelet effects of omega-aminoalkoxylxanthones.

A series of omega-aminoalkoxylxanthones were synthesized and tested in-vitro for their ability to inhibit aggregation of rabbit washed platelets and human platelet-rich plasma (PRP) induced by various inducers. Nine of these compounds showed more potent antiplatelet effects than natural norathyriol tetraacetate on collagen-induced aggregation. The various omega-aminoalkoxyl side chains of the synthesized compounds modified the antiplatelet effects. All the compounds tested in human PRP showed significant inhibition of secondary aggregation induced by adrenaline, suggesting that the antiplatelet effects of these compounds is mainly due to an inhibitory effect on thromboxane formation. These compounds at high concentration also cause vasorelaxing action in rat thoracic aorta.

Animals↗

PubMed1995

Vasodilator agents modulate rat glomerular mesangial cell growth and collagen synthesis.

Mesangial cell activation and extracellular matrix accumulation are hallmarks of many forms of glomerulonephropathy. We investigated the effect of several agents possessing vasodilating activities on rat mesangial cell growth and collagen synthesis. Using cell counting and a modified MTT assay, it was shown that dipyridamole, pentoxifylline, dicentrine, prazosin and doxazosin all caused a dose-dependent inhibition of serum-stimulated rat mesangial cell proliferation. Platelet-derived growth factor-induced cell proliferation was also inhibited by doxazosin and pentoxifylline. Dipyridamole and pentoxifylline inhibited collagen synthesis in confluent mesangial cells while dicentrine and doxazosin did not. The procollagen alpha 1 (I) mRNA expression was also decreased by dipyridamole and pentoxifylline. These results suggested that, in addition to dipyridamole, pentoxifylline and alpha 1-adrenoceptor blockers may have a potential to delay the progression of chronic glomerulopathy associated with mesangial proliferation.

Analysis of Variance↗

PubMed1995

Effects of dicentrine on the mechanical properties of systemic arterial trees in dogs.

We evaluated the effects of dicentrine on the physical properties of systemic arterial trees. Dicentrine, isolated from Lindera megaphylla, was identified as a potent, selective alpha 1-adrenoceptor antagonist. We used high-fidelity multisensor catheter to measure the ascending aortic pressure and flow signals in 9 mongrel dogs. A succinct T-tube model with vascular nonuniformity was adopted to relate the pulsatile pressure and flow waves. The model-estimated parameters were capable of representing the mechanical properties of the blood vessel walls. Dicentrine had a beneficial effect on the rigidity of head and body circulation, respectively. There were great improvements not only in the tube distensibility and wave transmission time, but also in the peripheral load compliance and resistance. In global circulation that was defined as the parallel combination of head and body circulation, dicentrine significantly reduced values in characteristic impedance of the ascending aorta from 164 +/- 67 to 105 +/- 43 dynes/s/cm5, and in wave reflection factor from 0.46 +/- 0.14 to 0.36 +/- 0.13, and in total peripheral vascular resistance from 4,751 +/- 1,226 to 3,581 +/- 1,277 dynes/s/cm5. On the other hand, total peripheral load compliance was increased from 0.2950 +/- 0.1794 to 0.4457 +/- 0.2199 ml/mm Hg. Cardiac output (CO) and heart rate (HR) remained unchanged, however. Dicentrine had an impact on the mechanical properties of Windkessel vessels and resistance vessels in the systemic circulation.

Adrenergic alpha-Antagonists↗

PubMed1994

YC-1, a novel activator of platelet guanylate cyclase.

YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped platelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5-trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo.

1-Methyl-3-isobutylxanthine↗

PubMed1994

Protracted treatment with phorbol ester modulates J-7 human hepatoma-cell-induced aggregation and coagulation of human platelet-rich plasma.

In heparinized human platelet-rich plasma (PRP), J-7 human hepatoma cells initially induced platelet aggregation; then a clot formed. ADP-scavenger systems, apyrase and creatine phosphate/creatine phosphokinase did not inhibit this tumor-cell-induced platelet aggregation (TCIPA), whereas hirudin and concanavalin A completely blocked it. J-7 cells also shortened the recalcification time of normal and of Factor-VIII- and IX-deficient human plasma, although it was inactive in shortening the recalcification time of Factor-VII-deficient plasma. After treatment with phorbol 12,13-dibutyrate (PDBu) for 5 to 90 min, the aggregation and coagulation abilities of J-7 cells were unaffected. Prolonged treatment of J-7 cells with PDBu but not with alpha-PDBu for 24 and 72 hr resulted in gradual loss of aggregation and coagulation. Staurosporine antagonized the effect of PDBu and restored aggregation and coagulation in J-7 cells. Protracted treatment with PDBu (24 or 72 hr) did not affect adherence of J-7 cells to the extracellular-matrix proteins (i.e., fibrinogen, fibronectin, laminin, vitronectin and collagen types I and IV) or to the surface of plastic culture dishes. The treatment also did not affect J-7 cell detachment from plastic culture dishes. These in vitro results demonstrate that protracted phorbol ester treatment diminishes TCIPA and blood coagulation of tumor cells.

Alkaloids↗

PubMed1994

Functional identification of alpha 1-adrenoceptor subtypes in human prostate: comparison with those in rat vas deferens and spleen.

The effects of some alpha 1-adrenoceptor antagonists (prazosin, nonselective for the alpha 1A- and alpha 1B-adrenoceptor subtypes; 5-methyl-urapidil, selective for the alpha 1A-adrenoceptor subtype; chloroethylclonidine, selective for the alpha 1B-adrenoceptor subtype) and nifedipine were compared on contractile responses to noradrenaline or phenylephrine in human prostatic tissues, rat vas deferens and spleen. In rat vas deferens, nifedipine (1 microM), but not chloroethylclonidine (100 microM), almost completely abolished noradrenaline-induced contraction, the pA2 values for prazosin and 5-methyl-urapidil against noradrenaline being 9.29 and 8.55, respectively. In rat spleen, chloroethylclonidine reduced (by 57%) the maximum contraction induced by phenylephrine; nifedipine was ineffective. The log concentration-response curve was shifted significantly to the right; the pA2 values of prazosin and 5-methyl-urapidil against phenylephrine were 9.45 and 7.21, respectively. In human prostatic tissues, both nifedipine and chloroethylclonidine produced significant inhibition of noradrenaline-induced contractions. Chloroethylclonidine produced a 44% reduction of the maximum contraction to noradrenaline and shifted the log concentration-response curve to the right. In contrast, nifedipine, while reducing the maximum response to a similar extent, produced a small rightward shift in the log concentration-response curve. The pA2 values for prazosin and 5-methyl-urapidil against noradrenaline were 9.21 and 7.74, respectively. The pA2 values for prazosin in these three tissues did not vary significantly, whereas that for 5-methyl-urapidil in human prostatic tissue was intermediate between that in rat vas deferens and that in rat spleen: these tissues contain primarily alpha 1A- and alpha 1B-adrenoceptor subtypes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1994

Antiplatelet effects of clausine-D isolated from Clausena excavata.

Clausine-D inhibited concentration-dependently the aggregation and release reaction of washed rabbit platelets induced by arachidonic acid and collagen, without affecting those induced by U46619, PAF and thrombin. The IC50 values of clausine-D on arachidonic acid- and collagen-induced platelet aggregation were calculated to be 9.0 +/- 1.1 and 58.9 +/- 0.9 microM, respectively. Thromboxane B2 and prostaglandin D2 formation in platelets caused by arachidonic acid were also suppressed. Clausine-D inhibited increased intracellular concentration of calcium in platelets caused by arachidonic acid and collagen, and also abolished the generation of inositol monophosphate caused by arachidonic acid, but not that by collagen, U46619, PAF and thrombin. In human citrated platelet-rich plasma, clausine-D inhibited the secondary phase, but not the primary phase, of aggregation induced by epinephrine and ADP. These results indicate that the antiplatelet effect of clausine-D is due to inhibition of the formation of thromboxane A2.

Adenosine Diphosphate↗

PubMed1994

Inhibition of cyclooxygenase activity and increase in platelet cyclic AMP by girinimbine, isolated from Murraya euchrestifolia.

Girinimbine is an antiplatelet agent isolated from Murraya euchrestifolia. In washed rabbit platelets, it inhibited arachidonic acid (AA)-, collagen-, U46619- and platelet-activating factor (PAF)-induced aggregation and ATP release in a concentration-dependent manner with IC50 values of 9.1 +/- 1.5, 16.7 +/- 1.7, 60.0 +/- 5.1 and 71.9 +/- 5.6 microM, respectively. However, it did not apparently affect thrombin-induced aggregation and ATP release even when a concentration of 80 microM was used. In citrated human platelet-rich plasma (PRP), girinimbine selectively inhibited secondary aggregation and ATP release without appearing to affect the primary aggregation induced by epinephrine and ADP. The formation of both platelet thromboxane B2 (TxB2) and prostaglandin D2 (PGD2) caused by AA was inhibited by girinimbine concentration dependently, with a maximal effect at 20 microM. Girinimbine also inhibited cyclooxygenase activity as reflected by the attenuation of prostaglandin E2 (PGE2) formation after incubation of sheep vesicular gland microsomes with arachidonic acid. In myo-[3H]inositol-labeled and fura-2-loaded platelets, [3H]inositol monophosphate generation and the increase in intracellular Ca2+ ([Ca2+]i) stimulated by AA and collagen, but not that stimulated by U46619, PAF and thrombin, were inhibited by girinimbine (20 microM). Platelet cyclic AMP levels were elevated by high concentrations of girinimbine (20 and 80 microM). These data indicate that the antiplatelet effect of girinimbine is due to the inhibition of cyclooxygenase activity and elevation of the cyclic AMP level.

Adenosine Triphosphate↗

PubMed1994

The effect of 3-[2-(cyclopropylamino)ethoxy]xanthone on platelet thromboxane formation.

A synthetic xanthone derivative, 3-[2-(cyclopropylamino)ethoxy] xanthone (CPEX), was investigated for its antiplatelet activities in washed rabbit platelets and human platelet-rich plasma. CPEX inhibited concentration-dependently the aggregation and ATP release of rabbit platelets caused by arachidonic acid (AA; 100 microM) and collagen (10 micrograms/ml), but not those by thrombin (0.1 U/ml), PAF (2 ng/ml), and U46619 (1 microM). The IC50 value of CPEX on AA-induced aggregation was 10.9 +/- 2.1 microM (n = 7). Thromboxane B2 formations caused by AA, collagen, and thrombin were inhibited by CPEX (20 microM), and prostaglandin D2 formation caused by AA was also inhibited. In human platelet-rich plasma, CPEX specifically inhibited the secondary aggregation and the release reaction induced by epinephrine (5 microM) and ADP (3 microM). CPEX also inhibited AA- and collagen-induced inositol-phosphate formation in [3H]myo-inositol-labeled platelets and intracellular Ca2+ increase in fura-2/AM-loaded platelets, respectively, without affecting those induced by PAF, thrombin, and U46619 in the presence of indomethacin (5 microM). These data suggest that the antiplatelet effect of CPEX is due to an inhibitory effect on the cyclooxygenase and then leads to the decrease of thromboxane formation.

Adenosine Triphosphate↗

PubMed1994

Cinnamophilin, a novel thromboxane A2 receptor antagonist, isolated from Cinnamomum philippinense.

The pharmacological activity of cinnamophilin ((8R,8'S)-4,4'-dihydroxy-3,3'-dimethoxy-7-oxo-8,8'-neolignan), isolated from Cinnamomum philippinense, was studied in isolated rat aorta, guinea-pig trachea and rabbit platelets. Cinnamophilin was found to be a thromboxane A2 receptor blocking agent in these tissues as revealed by its competitive antagonism of the U-46619 (9,11-dideoxymethanoepoxy-9 alpha,11 alpha-prostaglandin F2 alpha)-induced contraction of rat aorta and guinea-pig trachea and aggregation of rabbit platelets with pA2 values of 7.3 +/- 0.2, 5.2 +/- 0.1 and 6.3 +/- 0.3, respectively. Protection against the irreversible vasoconstriction of rat aorta caused by U-46619 (0.05 microM) was obtained by cinnamophilin (10 microM) but not by caffeine (25 mM). Cinnamophilin (1-15 microM) also possessed voltage-dependent Ca2+ channel blocking action, judging from its antagonism of the high K+ (60 mM)- and Bay K 8644 (0.1 microM)-induced contraction in rat thoracic aorta. Cinnamophilin (30 microM) produced a slight relaxation of noradrenaline (3 microM)-induced tonic contractions, and this relaxing effect was abolished in the presence of nifedipine (1 microM). Nifedipine (10 microM) sufficient to inhibit high K(+)-induced contractions failed to attenuate the contractile response to U-46619. A high concentration of cinnamophilin (100 microM) did not affect the aortic contraction induced by endothelin-1, angiotensin II, carbachol or serotonin. Neither cAMP nor cGMP in rat aorta was increased by cinnamophilin. These results indicate that cinnamophilin is a selective thromboxane A2 receptor antagonist especially in rat aorta, and also possesses voltage-dependent Ca2+ channel blocking properties.

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

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

gamma-Pyrone compounds. 5. Synthesis and antiplatelet effects of xanthonoxypropanolamines and related compounds.

A series of simple xanthonoxypropanolamines and related compounds were synthesized. 3-[3-(Cyclopropylamino)propoxy]-xanthone showed same potent antiplatelet effects as norathyriol tetraacetate on arachidonate-induced aggregation. 3-[3-(Cyclohexylamino)-2-hydroxypropoxy]xanthone showed more potent antiplatelet effects than norathyriol tetraacetate on collagen-induced aggregation. The various amino groups of the oxypropanolamine or oxypropylamine side chains of the synthesized compounds regulated the antiplatelet effects.

Animals↗

PubMed1994

The relaxant action of osthole isolated from Angelica pubescens in guinea-pig trachea.

The effect of osthole, isolated from Angelica pubescens, on the contraction of guinea-pig trachea was studied. Osthole (25-100 mumol/l), theophylline (10-1000 mumol/l) and higher concentrations of nifedipine (0.1-100 mumol/l) suppressed the contraction response curves of tracheal smooth muscle caused by carbachol, prostaglandin F2 alpha (PGF2 alpha), U46619 (thromboxane A2 analogue) and leukotriene C4 (LTC4) in a concentration-dependent manner. The contraction caused by high K+ (120 mmol/l) and cumulative concentrations of CaCl2 (0.03-3 mmol/l) was also inhibited concentration-dependently by osthole (25-100 mumol/l), theophylline (10-1000 mumol/l) and lower concentrations of nifedipine (0.01-0.1 mumol/l). The relaxant actions of osthole were not affected by propranolol (1 mumol/l), glibenclamide (10 mumol/l) or removal of tracheal epithelium. Osthole (100 mumol/l) was still effective in causing tracheal relaxation in the presence of nifedipine (1 mumol/l). In Ca(2+)-free- and EGTA (0.2 mmol/l)-containing medium, the relaxing effect of osthole was more potent than in normal Krebs solution. Osthole (25 and 50 mumol/l) caused 2.9 and 6.5, or 3.0 and 5.6 fold, respectively, increase in potency of forskolin or sodium nitroprusside in causing tracheal relaxation but did not affect that by cromakalim. Osthole (50 mumol/l) enhanced the increase in tissue cAMP and cGMP levels induced by forskolin and sodium nitroprusside, respectively, and in higher concentrations (100 and 250 mumol/l), itself increased markedly tissue cAMP and cGMP contents. Osthole (10-250 mol/l) inhibited the activity of cAMP and cGMP phosphodiesterases in a concentration-dependent manner. It is concluded that osthole exerts a non-specific relaxant effect on the trachealis by inhibiting the cAMP and cGMP phosphodiesterases.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

Antiplatelet constituents of formosan Rubia akane.

A known steroid, in addition to triterpenoids, anthraquinones, naphthalenes and a new anthraquinone glycoside, xanthopurpurin 3-O-beta-D-glucoside, were isolated from the roots of Rubia akane grown in Taiwan. Mollugin, a naphthohydroquinone, showed strong inhibition of arachidonic acid (AA)-induced and collagen-induced platelet aggregation. In contrast, 2-methyl-1,3,6-trihydroxyl-9,10-anthraquinone, xanthopurpurin 3-O-beta-D-glucoside, and xanthopurpurin showed mainly strong inhibition of collagen-induced platelet aggregation.

Animals↗