Biomedical subjects

Y X Wang

Publications and source records attributed to Y X Wang.

At least 19 recordsLinked to original sources

PubMed1992

Characteristics of depressing effect of cycloprotobuxine-A on the maximal velocity of depolarization in myocardium.

The characteristics of the depressing effect of cycloprotobuxine-A on Vmax in isolated guinea pig myocardium were investigated with a standard microelectrode technique. Cycloprotobuxine-A 3-30 mumol/l produced a concentration-dependent decrease in Vmax, associated with a prolongation of the action potential duration. At 3 mumol/l, a small resting block of Vmax, but a pronounced use-dependent block was found. This use-dependent block increased progressively as stimulation frequency increased from 0.5 to 4.0 Hz. The time constant and rate for onset of use-dependent block were 2.0-7.3 s and 0.11-0.25 AP-1 (reciprocal action potential number), respectively. The time constant and half-life for recovery from use-dependent block were 11.8 and 8.1 s. Thus, the kinetics of the depressing effect of cycloprotobuxine-A on Vmax were intermediate. In muscles depolarized by high [K+]0, the resting block was enhanced slightly, while use-dependent block was greatly augmented. These results suggested that cycloprotobuxine-A could have a low affinity for resting Na+ channels but a much higher affinity for activated and/or inactivated Na+ channels, and that the use-, frequency- and voltage-dependent effects of cycloprotobuxine-A on Vmax may play an important role in preventing the development of cardiac arrhythmias.

Action Potentials↗

PubMed1992

Mechanism of the vasodilator action of calcitonin gene-related peptide in conscious rats.

1. The aim of this study was to investigate whether the hypotensive effect of rat alpha-calcitonin gene-related peptide (alpha CGRP) in conscious rats is mediated by endothelium-derived nitric oxide (NO) or the opening of adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels. 2. Dose-mean arterial pressure (MAP)-response curves of alpha CGRP were examined in the presence of vehicle, phenylephrine, KATP channel antagonist glibenclamide or NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-D-arginine methyl ester (D-NAME). Dose-MAP-response curves for sodium nitroprusside were also constructed in the presence and absence of L-NAME and D-NAME. 3. alpha CGRP and nitroprusside produced dose-dependent reductions in MAP which were potentiated by phenylephrine. Both L-NAME and D-NAME attenuated the depressor response to alpha CGRP but not nitroprusside. 4. Dose-MAP-response curves for pinacidil, a KATP-channel activator, were also examined in the presence of glibenclamide or vehicle. Glibenclamide attenuated pinacidil- but not alpha CGRP-induced reductions in MAP. 5. It is concluded that the hypotensive effects of alpha CGRP are partially mediated via endothelium-derived NO but not via the opening of KATP channels.

Adenosine Triphosphate↗

PubMed1992

Effects of anaesthetic agents on pressor response to beta-blockers in the rat.

It has been shown that paradoxical pressor response to a beta-adrenoceptor antagonist occurs in conscious rats pretreated with an alpha-adrenoceptor antagonist. This study examines the influence of anaesthetic agents on mean arterial pressure (MAP) response to a beta-blocker. Cumulative dose-response curves of propranolol (non-selective), ICI 118,551 (beta 2-selective) and atenolol (beta 1-selective) were constructed in phentolamine-treated rats anaesthetized with urethane, pentobarbitone or halothane. I.v. injections of all three beta-blockers caused dose-dependent increases in MAP in urethane-anaesthetized rats. In halothane-anaesthetized rats, propranolol and atenolol did not alter MAP while ICI 118,551 caused a small dose-dependent increase in MAP. In the presence of pentobarbitone, none of the beta-blockers raised MAP. In the second series of experiments, a single i.v. bolus dose of propranolol was given in phentolamine-treated rats anaesthetized with pentobarbitone, amobarbitone, ketamine or chloralose. Propranolol did not affect MAP in rats anaesthetized with pentobarbitone, amobarbitone and chloralose but it partially reversed the hypotensive effect of phentolamine in ketamine-anaesthetized rats. In the third series, propranolol or atenolol was i.v. injected in pentobarbitone-anaesthetized rats treated with both phentolamine and adrenaline. Both propranolol and atenolol raised MAP. Our results show that anaesthetic agents differentially affect the MAP response to a beta-blocker.

Adrenergic beta-Antagonists↗

PubMed1992

Synthesis of cell-impermeable Cl-sensitive fluorescent indicators with improved sensitivity and optical properties.

Quinolinium compounds have been used as Cl-sensitive fluorescent indicators in cells and cell-free membrane fractions. To improve Cl sensitivity and for conjugation via nucleophilic reaction, the compounds 6-methoxy-N-(n-aminoalkyl)quinolinium bromide hydrochloride (AAQ) with alkyl chain lengths (n) of 2 (AEQ), 3 (APQ), and 4 (ABQ) were synthesized. AAQ was water soluble, fluorescent, and quenched by Cl. The Stern-Volmer constants (KCl) for quenching of protonated AEQ, APQ and ABQ by Cl were 354, 322, and 272 M-1, respectively, higher than KCl for 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ; 118 M-1). To eliminate pH-dependent fluorescence, 6-methoxy-N-(3-trimethylammoniumpropyl)quinolinium dibromide (TMAPQ) was synthesized (KCl, 310 M-1). To red shift fluorescence excitation and emission spectra, 6-phenyl-N-(3-trimethylammoniumpropyl)quinolinium dibromide (phenyl-TMAPQ) (emission 475 nm) and N-(3-trimethylammoniumpropyl)phenanthridinium dibromide (TMAPP) (excitation 380 nm) were synthesized. AEQ and ABQ were conjugated with neutral dextran activated by cyanogen bromide to give indicator-to-dextran mole ratios of 5 to 20. KCl values at pH 7.4 were 132 (AEQ-dextran) and 237 M-1 (ABQ-dextran). To construct a single molecule with Cl-sensitive and insensitive moieties, the bichromophores 6-methoxy-N-(n- dansylsulfonamidoalkyl)quinolinium with alkyl chains of two and four were synthesized. The new Cl-sensitive indicators were used for measurement of intracellular Cl activity and for the labeling of endocytic vesicles in 3T3 fibroblasts and T84 cells. Our results indicate that N-substitution of quinoline with positively charged moieties gives increased Cl sensitivity, and extension of ring conjugation gives indicators with red-shifted fluorescence spectra.

Cell Membrane Permeability↗

PubMed1992

Dopamine DA1 receptor agonist, fenoldopam, reverses glycine-induced hyperfiltration in rats.

Stimulation of dopamine DA1 receptors can prevent glomerular hyperfiltration in streptozotocin-induced diabetic rats. In the present study we have therefore investigated whether the DA1 agonist, fenoldopam, can prevent glycine-induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate clearances in conscious chronically instrumented rats. Glycine (3.7 mg/min iv; n = 8) significantly increased GFR by 37% (from 1.09 +/- 0.53 to 1.49 +/- 0.11 ml.100 g-1.min-1, P less than 0.01), ERPF by 23% (from 2.96 +/- 0.30 to 3.64 +/- 0.43 ml.100 g-1.min-1, P less than 0.05), and filtration fraction (FF) by 13% (from 0.39 +/- 0.04 to 0.44 +/- 0.05, P less than 0.05). Fenoldopam, at a dose (1 microgram.kg-1.min-1 iv; n = 8) that increased ERPF by 26%, decreased FF by 13%, but did not change GFR, significantly attenuated the glycine-induced hyperfiltration. In the presence of fenoldopam, glycine resulted in only an 8% increase in GFR (from 1.08 +/- 0.07 to 1.17 +/- 0.09 ml.100 g-1.min-1; n = 8). ERPF increased by 20% (from 3.34 +/- 0.24 to 4.00 +/- 0.21 ml.100 g-1.min-1, P less than 0.05), and FF decreased by 13% (from 0.34 +/- 0.03 to 0.29 +/- 0.02, P less than 0.05). Infusion of the DA1-selective antagonist, Sch 23390, abolished the effects of fenoldopam. Thus DA1 receptor activation can prevent glomerular hyperfiltration induced by glycine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Inhibition of nitric oxide, bradykinin, and prostaglandins in normal rats.

We assessed the vasodilator effect of endothelium-derived nitric oxide by inhibiting its formation with NG-monomethyl L-arginine (LNMMA) on systemic and regional hemodynamics in conscious, normotensive rats, using the radioactive microsphere technique. In rats injected with 10 mg/kg LNMMA (n = 8), mean blood pressure increased by 16.2 +/- 2.6 mm Hg, and heart rate decreased by 54.3 +/- 16.7 beats per minute. In comparison with rats injected with 5% dextrose (n = 14), cardiac index was lower by 35.6% (p less than 0.01), and total peripheral vascular resistance was higher by 51.6% (p less than 0.01); regional blood flows were lower and vascular resistance higher in most organs. Changes were significant in the heart, kidney, stomach, large intestine, skin, and adrenals (p less than 0.05). Preinjection of 100 mg/kg L-arginine prevented the pressor response but only partially attenuated the other hemodynamic effects of LNMMA. Combination of LNMMA with the bradykinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg)trifluoroacetic acid (50 micrograms/min for 5 minutes) did not produce systemic or regional effects different from those obtained with LNMMA alone. Combination of LNMMA with indomethacin (10 mg/kg) resulted in additional changes in the cerebral circulation, blood flow decreasing by an additional 44.2% (p less than 0.01) and vascular resistance increasing by 75.3% (p less than 0.01) compared with changes produced by LNMMA alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The effect of zidovudine treatment on serum neopterin and beta 2-microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals.

Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV) infection were included in a double-blind, randomized, placebo-controlled trial of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to evaluate changes in the serum immune activation markers neopterin and beta 2-microglobulin (beta 2M) as early markers of the antiviral effect of zidovudine on HIV type 1 (HIV-1) infection. The mean values of serum neopterin and beta 2M levels in 27 placebo-treated subjects tended to increase with time. The mean value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction was seen at 8 weeks of treatment (10.78 nmol/L, p less than 0.0001). Subsequently, the mean value of serum neopterin increased but remained below the pretreatment value for more than a year. Serum beta 2M levels decreased (from 3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean beta 2M level returned to pretreatment value at approximately 24 weeks of the treatment. There was a close correlation between changes from baseline in serum neopterin and beta 2M during the first 16 weeks of the zidovudine therapy, but not later. Subjects with greater reductions of serum neopterin or beta 2M tended to maintain lower levels of these markers with continued zidovudine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

PubMed1992

Protective effect of cycloprotobuxine-A against cardiac arrhythmias induced by ouabain.

Cycloprotobuxine-A (CPB-A) 1-4 mg.kg-1 iv increased the dose of ouabain required to induce ventricular arrhythmias in guinea pigs. At the equitoxic doses (1/50 LD50), CPB-A was more potent than cyclovirobuxine-D and amiodarone. Pretreatment with reserpine (5 mg.kg-1 ip), vagotomy or pithing spinal cord did not prevent the action of CPB-A, which indicate that the protective effect of CPB-A may be due to its direct action on myocardium without the involvement of nervous system. In isolated guinea pig ventricular muscles, CPB-A 3 mumol.L-1 consistently decreased the amplitude of oscillatory afterpotentials (OAP) and blocked triggered activity elicited by ouabain. At 30 mumol.L-1, CPB-A abolished the appearance of OAP. It seems that one of the mechanisms for the anti-arrhythmic action of CPB-A was a decrease in the amplitude of OAP.

Alkaloids↗

PubMed1992

The role of adenosine in glycine-induced glomerular hyperfiltration in rats.

Ingestion of a high-protein diet or infusion of amino acids induces glomerular hyperfiltration and hyperemia. We have investigated the role of endogenous adenosine in glycine-induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in conscious chronically instrumented rats. Glycine (3.7 mg/min, i.v.; n = 6) significantly increased GFR and ERPF from 0.92 +/- 0.07 to 1.13 +/- 0.08 and 3.28 +/- 0.24 to 3.69 +/- 0.19 ml/min.100 g, respectively. In the presence of adenosine deaminase (ADA, 2 U/kg.min, n = 6), glycine-induced glomerular hyperfiltration and hyperemia were blunted. The small changes in GFR (from 0.86 +/- 0.06 to 0.90 +/- 0.10 ml/min.100 g) and ERPF (from 3.60 +/- 0.57 to 3.83 +/- 0.53 ml/min x 100 g) were not statistically significant. Erythro-9-(2-hydroxy-3-nonyl) adenosine hydrochloride (100 micrograms/kg.min, n = 6), an ADA inhibitor, reversed the effect of ADA. Injection of 8-phenyltheophylline (10 mg/kg, n = 6), an adenosine A1 receptor antagonist that alone did not affect GFR, abolished the glycine-induced glomerular hyperfiltration (GFR from 1.02 +/- 0.08 to 0.93 +/- 0.08 ml/min.100 g, P > .05). 8-phenyltheophylline, which itself decreased ERPF, also significantly decreased the ERPF response to glycine (3.47 +/- 0.26 to 2.78 +/- 0.14 ml/min x 100 g). Thus, endogenous adenosine, acting at adenosine A1 receptors, plays an important role in the glomerular hyperfiltration and hyperemia induced by glycine.

Adenosine↗

PubMed1992

Eleven lymphoid phenotypic markers in HIV infection: selective changes induced by zidovudine treatment.

HIV infection induces substantial changes in the expression of many lymphocyte phenotypic markers as well as depletion of CD4 lymphocyte numbers. A comprehensive study was undertaken to determine whether seven lymphocyte phenotypic changes associated with HIV infection (increased CD38, HLA-DR, CD57, and CD71 and decreased CD11b, CD45RA, and leu-8) are altered by zidovudine (ZDV) administration. Levels of the four major lymphoid subsets (CD4, CD8, B, and NK cells) and changes in the serum activation markers neopterin and beta 2-microglobulin (beta 2M) were also measured. Elevated pretreatment expression of CD38 and CD71 was reduced significantly toward normal at 2 weeks by ZDV; however, CD38 and CD71 returned to pretreatment levels at different rates. The kinetics of CD38 reduction and the return to pretreatment levels were similar to those of serum neopterin and beta 2M. HLA-DR decreased in many but not all subjects. CD4 lymphocytes showed a transient increase, most evident at 8 weeks of treatment. Lymphoid phenotypes that did not show significant changes after ZDV therapy included CD57, CD11b, CD45RA, and leu-8 markers as well as CD8 T cells, CD20 B cells, and CD56 NK cells. The fact that some lymphocyte phenotypic markers change toward normal with ZDV treatment and others do not indicates that complex processes underlie immune perturbations of HIV infection. Several phenotypic markers (CD38, CD71, and HLA-DR) that are susceptible to short-term effects of ZDV (but with changes that differ from CD4 T cell changes) are surrogate marker candidates for evaluation in anti-HIV treatment.

Biomarkers↗

PubMed1992

Comparison of systemic and regional hemodynamic effects of a diuretic, an angiotensin II receptor antagonist, and an angiotensin-converting enzyme inhibitor in conscious renovascular hypertensive rats.

The present experiments were designed to compare the antihypertensive action and the systemic and regional hemodynamic effects of a diuretic (furosemide), an angiotensin II (AngII) receptor blocker (Dup 753), and an angiotensin converting enzyme (ACE) inhibitor (enalapril) in conscious, two-kidney, one-clip renovascular hypertensive rats by the radioactive microsphere technique. Measurements were done 3 hours after a single dose treatment. Furosemide (20 mg/kg) produced a marked diuresis and tachycardia with no change in blood pressure; in comparison with control rats, furosemide-treated rats had total peripheral vascular resistance increased by 46.55% (p less than 0.01) and local vascular resistance increased in most organs, to a significant degree in the spleen, muscle, stomach, intestine, and skin (p less than 0.05 to 0.01). Dup 753 (20 mg/kg) and enalapril (10 mg/kg) decreased mean blood pressure by 41.89 +/- 7.17 mm Hg and 47.13 +/- 8.67 mm Hg, respectively (p less than 0.01), with tachycardia only in the Dup 753 group. Total peripheral and local vascular resistances in several tissues were significantly lower in both the Dup 753 and enalapril groups than in the furosemide group. In particular, both antiangiotensin agents, in contrast to furosemide, produced significant decrease in renal vascular resistance by 42.28% and 38.81%, respectively (p less than 0.01), with a tendency to increase the renal blood flow (of the intact kidney). No detectable differences were found in systemic and regional hemodynamic changes between the Dup 753 and enalapril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Renin-angiotensin system inhibition reduces glycine-induced glomerular hyperfiltration in conscious rats.

It has been reported that high protein intake or amino acid infusion-induced glomerular hyperfiltration are accompanied by an elevation of plasma renin activity and renal renin mRNA. We therefore investigated the effect of inhibition of the renin-angiotensin system by SK&F 108566, a novel, nonpeptide angiotensin II (AII) receptor antagonist, or by enalapril, an angiotensin converting enzyme inhibitor, on glycine-induced hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate clearances in conscious chronically instrumented rats. Glycine infusion (3.7 mg/min i.v.; n = 8) significantly increased GFR by 27% (from 1.09 +/- 0.53 to 1.38 +/- 0.08 ml/min.100 g), ERPF by 22% (2.96 +/- 0.30 to 3.61 +/- 0.32 ml/min.100 g) and significantly decreased effective renal vascular resistance by 22% [from 25.4 +/- 2.9 to 20.8 +/- 2.5 mm Hg/(ml/min.100 g)]. SK&F 108566 (30 micrograms/kg.min) or enalapril (1 mg/kg), at doses which inhibited the pressor effects of AII or AI, respectively, but had no significant influence on base-line GFR and ERPF, significantly attenuated the glycine-induced glomerular hyperfiltration and hyperemia. In the presence of SK&F 108566 or enalapril, glycine resulted in only small, statistically insignificant changes in GFR (from 1.07 +/- 0.03 to 1.10 +/- 0.04 and from 1.19 +/- 0.03 to 1.21 +/- 0.08 ml/min.100 g, respectively), ERPF (from 3.27 +/- 0.21 to 3.53 +/- 0.26 and from 3.57 +/- 0.11 to 3.41 +/- 0.38 ml/min.100 g, respectively) and effective renal vascular resistance [from 21.2 +/- 1.9 to 19.2 +/- 1.6 and from 18.4 +/- 0.9 to 20.2 +/- 2.2 mm Hg/(ml/min.100 g], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylates↗

PubMed1991

Pressor effects of L and D enantiomers of NG-nitro-arginine in conscious rats are antagonized by L- but not D-arginine.

The effects of NG-nitro-L-arginine (L-NNA) and NG-nitro-D-arginine (D-NNA) on mean arterial pressure (MAP) were studied in conscious, unrestrained rats. I.v. bolus of either L-NNA (1-64 mg/kg) or D-NNA (2-64 mg/kg) dose dependently increased MAP to similar maximum values of 55 +/- 7 and 52 +/- 4 mm Hg and with ED50 values of 4.0 +/- 0.9 and 8.9 +/- 1.2 mg/kg (P less than 0.05), respectively. The time course of the MAP response to a single dose (32 mg/kg i.v. bolus) of L-NNA and D-NNA were also obtained. The pressor effects of L-NNA and D-NNA each lasted greater than 2 h with the rise phase t 1/2 of 5 and 27 min (P less than 0.05), respectively. I.v. infusions (10 mg/kg per min) of L-arginine (L-Arg) and D-arginine (D-Arg) did not alter the pressor response to noradrenaline nor angiotensin II. L-Arg but not D-Arg attenuated the pressor responses to both L-NNA and D-NNA. Therefore, both L-NNA and D-NNA are efficacious and long-lasting pressor agents; the pressor effects of both can be antagonized by L-Arg but not D-Arg. Our results suggest that the pressor effects of both L-NNA and D-NNA involve the L-Arg/nitric oxide pathway.

Animals↗

PubMed1991

Effects of inhalation and intravenous anesthetic agents on pressor response to NG-nitro-L-arginine.

The effects of anaesthetic agents on pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, were examined in rats. I.v. bolus of L-NNA (1-32 mg/kg) in conscious rats dose dependently increased mean arterial pressure (MAP) to a maximum value of 53 +/- 2 mmHg at 16 mg/kg with ED50 value of 4.7 +/- 0.9 mg/kg. The effects of a single i.v. bolus dose (32 mg/kg) of L-NNA were examined in conscious rats and rats anaesthetised with pentobarbital, chloralose, ketamine, althesin (mixture of alphaxalone and alphadolone), urethane, enflurane or halothane. In conscious rats, peak MAP (51 +/- 3 mmHg) was reached 10 min after i.v. injection and the effect lasted more than two hours. The magnitudes of peak MAP differed under the influence of anaesthetic agents with the following rank order: althesin greater than conscious = pentobarbital = chloralose = ketamine = urethane greater than enflurane much greater than halothane (in which there was negligible change in MAP). The onsets were delayed in rats anaesthetised with pentobarbital, althesin, chloralose and enflurane but not altered with ketamine and urethane compared to that in conscious rats. Therefore, L-NNA caused intense and prolonged pressor response in conscious rats and rats anaesthetised with the i.v. anaesthetic agents pentobarbital, chloralose, ketamine, althesin and urethane. MAP effect of L-NNA was markedly attenuated by the inhalation anaesthetics halothane and enflurane.

Alfaxalone Alfadolone Mixture↗

PubMed1991

Functional water channels and proton pumps are in separate populations of endocytic vesicles in toad bladder granular cells.

Functional water channels are retrieved by endocytosis from the apical membrane of toad bladder granular cells in response to vasopressin [Shi, L.-B., & Verkman, A.S. (1989) J. Gen. Physiol. 94, 1101-1115]. To examine whether endocytic vesicles which contain the vasopressin-sensitive water channel fuse with acidic vesicles for entry into a lysosomal pathway, ATP-dependent acidification and osmotic water permeability were measured in endosomes from control bladders and bladders treated with vasopressin (VP) and/or phorbol myristate acetate (PMA). Endosomes were labeled with the fluid-phase markers 6-carboxyfluorescein or fluorescein-dextran. Osmotic water permeability (Pf) was measured by stopped-flow fluorescence quenching and proton ATPase activity by ATP-dependent, N-ethylmaleimide-inhibitable acidification. In a microsomal pellet, Pf was low (less than 0.002 cm/s, 20 degrees C) in labeled endocytic vesicles from control bladders but high (0.05-0.1 cm/s) in a subpopulation (50-70%) of vesicles from VP- and PMA-treated bladders. Following ATP addition, the average drop in pH was 0.1 (control), 0.3 (VP), and 0.2 (PMA) unit. Measurement of pH in individual endocytic vesicles by quantitative image analysis showed that less than 20% of vesicles from VP-treated bladders acidified by greater than 0.5 pH unit. To examine whether water channels and proton pumps were present in the same endocytic vesicles, the pH of endosomes with high and low water permeability was measured from the effect of ATP on the amplitude of the fluorescence quenching signal in response to an osmotic gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1991

PDGF A-chain gene is expressed by mammalian neurons during development and in maturity.

Platelet-derived growth factor (PDGF) may be a critical factor in the temporal differentiation of glial elements in the mammalian central nervous system. We have used in situ hybridization and immunoperoxidase staining to investigate the localization of PDGF A and have observed high levels of PDGF A-chain mRNA and immunoreactive PDGF A in neurons of embryonic and adult mice. PDGF A-chain expression was shown to be developmentally regulated and tissue specific. Every neuronal population examined in the central and peripheral nervous systems expresses PDGF A transcripts. Variable, significantly weaker signals are observed in glial cells. In contrast to known neurotrophic factors, the PDGF A transcripts are widely distributed among neurons. This generalized distribution of PDGF A transcripts, together with the known effects of PDGF on glial cells in vitro, suggests a unique role of neurons in regulating the proliferation and differentiation of glial cells in vivo.

Animals↗

PubMed1991

Expression and stability of amplified genes encoding 5-enolpyruvylshikimate-3-phosphate synthase in glyphosate-tolerant tobacco cells.

Two distinct cDNAs for 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) were obtained from a glyphosate-tolerant tobacco cell line. The cDNAs were 89% identical and the predicted sequences of the mature proteins were greater than 83% identical with EPSPS proteins from other plants. Tobacco EPSPS proteins were more similar to those from tomato and petunia than Arabidopsis. One cDNA clone, EPSPS-1, represented a gene that was amplified in glyphosate-tolerant cells, while the gene for EPSPS-2 was unaltered in these cells. Consequently, EPSPS-1 mRNA was more abundant in tolerant than unselected cells, whereas EPSPS-2 mRNA was at relatively constant levels in these cell lines. Exposure of unselected cells and tobacco leaves to glyphosate produced a transient increase in EPSPS mRNA. However, glyphosate-tolerant cells containing amplified copies of EPSPS genes did not show a similar response following exposure to glyphosate. A significant proportion of the EPSPS gene amplification was maintained when tolerant cells were grown in the absence of glyphosate for eight months. Plants regenerated from these cells also contained amplified EPSPS genes.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗

PubMed1991

Actions of lead on transmitter release at mouse motor nerve terminals.

The actions of lead (Pb2+) on transmitter release were studied at neuromuscular junctions in mouse diaphragm in vitro. The quantal content of end-plate potentials (EPPs) was reduced by Pb2+ in a dose-related manner consistent with inhibition of Ca2+ entry into nerve terminals, with a half-maximal effect at 1.4 microM (in 0.5 mM Ca2+ and 2 mM Mg2+). Pb2+ also inhibited the increased frequency of MEPPs (fMEPP where MEPPs denotes miniature EPPs) produced by Ba2+ in the presence of raised K+, blocking the calculated Ba2+ entry half-maximally at 170 microM. However, at concentrations of 50-200 nM, Pb2+ often increased fMEPP in 20 mM K+ in the presence of Ca2+ and acted to promote the irreversible effect of lanthanum (La3+) to raise fMEPP. In nominally Ca(2+)-free solution with 20 mM K+, brief (1 min) application of Pb2+ (20-320 microM) caused rapid dose-dependent reversible rises in fMEPP. With prolonged exposure to Pb2+, fMEPP rose and then slowly declined; after removal of Pb2+, once fMEPP had fallen to low levels, fMEPP responded nearly normally to Ca2+ or ethanol, but not to Pb2+ itself. In 5 mM K+, 0 mM Ca2+ and varied [Pb2+] (where [] denotes concentration), nerve stimulation caused no EPPs, but prolonged tetanic stimulation produced increases in fMEPP graded with [Pb2+] that persisted as a "tail"; results were consistent with growth of fMEPP with the 4th power of intracellular Pb2+ and removal of intracellular Pb2+ with a time constant of about 30 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗