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1.
Experiments were carried out in healthy male volunteers to investigate the effect of the inhalation of prostaglandin F2α (PGF2α) on airways resistance and the influence of the subsequent inhalation of prostaglandin E2 (PGE2). Airways resistance, which reflects the tone of smooth muscle in the larger airways in man, was measured by total body plethysmography.The inhalation of PGF2α (40-60 μg) caused an increase in airways resistance in all subjects. Both PGE2 (55 μg) and isoprenaline (550 μg) given by metered aerosol promptly reversed the bronchoconstriction induced by PGF2α, but isoprenaline was more effective in this respect.A role for these prostaglandins in the control of bronchial muscle tone is discussed. 相似文献
2.
Twenty patients with extrinsic type bronchial asthma are shown to have a significant fall in vital capacity (V.C.) and forced expiratory volume in 1 second (F.E.V.1) after an intravenous infusion of 50μg. of histamine dihydrochloride. In 10 of these subjects the fall in V.C. and F.E.V.1 produced by intravenous histamine is inhibited by the alpha-receptor blocking drugs phentolamine and phenoxybenzamine injected before the histamine test. The inhalation of disodium cromoglycate in 10 subjects is also shown to inhibit the fall in V.C. and F.E.V.1 produced by the intravenous infusion of histamine. It is suggested that bronchial smooth muscle in asthmatic subjects has alpha-adrenergic receptor sites, and that a possible mechanism for the action of disodium cromoglycate is that it stabilizes the cell membrane, thereby altering calcium ion transport. 相似文献
3.
The influence on airway conductance of inhaled aerosols of prostaglandin F2α (PGF2α), histamine, and prostaglandin E2 (PGE2) was studied in 10 patients with spirometrically reversible bronchial asthma and in 10 healthy subjects with no history of lung disorder. Both groups responded with bronchoconstriction after inhalation of PGF2α but the asthmatic patients were about 8,000 times more sensitive to the compound than were the healthy controls. In the patients, but not in the controls, PGF2α often caused a long-standing decrease in airway conductance with symptoms resembling allergen-provoked asthmatic attacks. On the other hand, the patients showed less than a 10-fold increase in sensitivity to histamine, and the ratio of histamine: PGF2α doses causing a 50% decrease of airway conductance was 2·6:1 and 2,400:1 in controls and patients respectively. Inhalation of PGE2 while moderately but consistently increasing airway conductance in controls, had a variable—occasionally slight bronchoconstrictive—effect in patients. The decrease in airway conductance by a given dose of PGF2α was little modified by the simultaneous inhalation of a 100-times higher PGE2 dose. It is suggested that endogenous, locally formed PGF2α may play an important part in the pathogenesis of bronchial asthma. 相似文献
4.
K. N. V. Palmer J. S. Legge W. F. D. Hamilton M. L. Diament 《BMJ (Clinical research ed.)》1970,2(5700):23-24
The effect of the aerosol inhalation of 200 μg. of salbutamol and 1,000 μg. of isoprenaline on spirometry and blood-gas tensions was compared in the same 11 asthmatic subjects. Both drugs significantly reduced airway obstruction, and the extent of the reduction did not differ for periods of up to 30 minutes. After isoprenaline tachycardia and a small significant fall in arterial oxygen tension occurred, whereas after salbutamol there was no change in pulse rate and the arterial oxygen tension did not fall. 相似文献
5.
In a double-blind trial of the effect of inhaling three different β-adrenergic stimulants (isoprenaline sulphate 1,000 μg., orciprenaline sulphate 1,500 μg., and salbutamol 200 μg.) and a placebo on ventilatory function in 24 patients with chronic asthma salbutamol was found to have a much longer action than isoprenaline, and it produced a slightly more intense and prolonged effect than orciprenaline. In a double-blind subjective assessment 13 of the 24 patients selected salbutamol as the most effective preparation, while only five preferred isoprenaline and three orciprenaline. Hence salbutamol, given by inhalation, may prove to be the most effective drug at present available for the short-term relief of asthmatic symptoms. 相似文献
6.
Ewa Nizankowska Angelita Q. Sheridan Marie H. Maile Carol J. Cross Rafal Nizankowski Krystyna Prochowska Andrew Szczeklik 《Prostaglandins & other lipid mediators》1985,29(3):349-362
We evaluated in a double-blind study the bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1 (PGE1-carbinol), described recently as a nonirritant bronchodilator in animals. Fifteen asthmatic patients received by inhalation single doses of 1, 10, and 30 μg PGE1-carbinol, 55 μg PGE2, and placebo (10% ethanol in normal saline, which was also used as diluent for the PGs). Such pulmonary function tests as forced expiratory volume in 1 second, forced vital capacity, and maximal expiratory flow were monitored during 2 hours following inhalation of each compound. 10 and 30 μg PGE1-carbinol produced significant but short-acting bronchodilation, similar to that caused by 55 μg PGE2. One-third of the patients reported mild cough and throat irritation during and shortly after inhalation of 30 μg PGE1-carbinol or 55 μg PGE2. Placebo and 1 μg PGE1-carbinol produced minimal side effects, but neither agent caused bronchodilation. In an adjunctive, unblinded trial, the same patients received 400 μg fenoterol. Fenoterol caused greater bronchodilation 15 and 30 minutes after inhalation than did the PGs in the double-blind study. 相似文献
7.
In asthma elevated rates of exhaled breath temperature changes (Δe°T) and bronchial blood flow (Qaw) may be due to increased vascularity of the airway mucosa as a result of inflammation.We investigated the relationship of Δe°T with Qaw and airway inflammation as assessed by exhaled nitric oxide (NO). We also studied the anti-inflammatory and vasoactive effects of inhaled corticosteroid and β2-agonist.Δe°T was confirmed to be elevated (7.27 ± 0.6 Δ°C/s) in 19 asthmatic subjects (mean age ± SEM, 40 ± 6 yr; 6 male, FEV1 74 ± 6 % predicted) compared to 16 normal volunteers (4.23 ± 0.41 Δ°C/s, p < 0.01) (30 ± 2 yr) and was significantly increased after salbutamol inhalation in normal subjects (7.8 ± 0.6 Δ°C/ s, p < 0.05) but not in asthmatic patients. Qaw, measured using an acetylene dilution method was also elevated in patients with asthma compared to normal subjects (49.47 ± 2.06 and 31.56 ± 1.6 μl/ml/min p < 0.01) and correlated with exhaled NO (r = 0.57, p < 0.05) and Δe°T (r = 0.525, p < 0.05). In asthma patients, Qaw was reduced 30 minutes after the inhalation of budesonide 400 μg (21.0 ± 2.3 μl/ml/min, p < 0.05) but was not affected by salbutamol.Δe°T correlates with Qaw and exhaled NO in asthmatic patients and therefore may reflect airway inflammation, as confirmed by the rapid response to steroids. 相似文献
8.
Dedmer Schaafsma Reinoud Gosens I Sophie T Bos Herman Meurs Johan Zaagsma S Adriaan Nelemans 《Respiratory research》2005,6(1):85
Background
In addition to their proliferative and differentiating effects, several growth factors are capable of inducing a sustained airway smooth muscle (ASM) contraction. These contractile effects were previously found to be dependent on Rho-kinase and have also been associated with the production of eicosanoids. However, the precise mechanisms underlying growth factor-induced contraction are still unknown. In this study we investigated the role of contractile prostaglandins and Rho-kinase in growth factor-induced ASM contraction.Methods
Growth factor-induced contractions of guinea pig open-ring tracheal preparations were studied by isometric tension measurements. The contribution of Rho-kinase, mitogen-activated protein kinase (MAPK) and cyclooxygenase (COX) to these reponses was established, using the inhibitors Y-27632 (1 μM), U-0126 (3 μM) and indomethacin (3 μM), respectively. The Rho-kinase dependency of contractions induced by exogenously applied prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) was also studied. In addition, the effects of the selective FP-receptor antagonist AL-8810 (10 μM) and the selective EP1-antagonist AH-6809 (10 μM) on growth factor-induced contractions were investigated, both in intact and epithelium-denuded preparations. Growth factor-induced PGF2α-and PGE2-release in the absence and presence of Y-27632, U-0126 and indomethacin, was assessed by an ELISA-assay.Results
Epidermal growth factor (EGF)-and platelet-derived growth factor (PDGF)-induced contractions of guinea pig tracheal smooth muscle preparations were dependent on Rho-kinase, MAPK and COX. Interestingly, growth factor-induced PGF2α-and PGE2-release from tracheal rings was significantly reduced by U-0126 and indomethacin, but not by Y-27632. Also, PGF2α-and PGE2-induced ASM contractions were largely dependent on Rho-kinase, in contrast to other contractile agonists like histamine. The FP-receptor antagonist AL-8810 (10 μM) significantly reduced (approximately 50 %) and the EP1-antagonist AH-6809 (10 μM) abrogated growth factor-induced contractions, similarly in intact and epithelium-denuded preparations.Conclusion
The results indicate that growth factors induce ASM contraction through contractile prostaglandins – not derived from the epithelium – which in turn rely on Rho-kinase for their contractile effects. 相似文献9.
Prostaglandin E2 (PGE2) (5 μg in 5 μl) injected into the third ventricle (3rd V) of intact or castrated conscious male rats markedly increased plasma LH titers 15 and 30 min after its injection. PGE1 injected at a similar dose slightly increased plasma LH in intact but not in orchidectomized rats. A small but significant increase in plasma FSH followed 3rd V injection of both PGE2 and PGE1 in intact but not in castrated rats. PGF1α and PGF2α were completely ineffective in modifying plasma LH or FSH titers in either intact or castrated rats. These results indicate that PGE2 and to a lesser extent PGE1 specifically stimulate gonadotropin release in the male rat, possibly by a direct action on the central nervous system. They also support the hypothesis that PGE2 and perhaps PGE1 play a physiological role in neural control of pituitary gonadotropin release. 相似文献
10.
P.J. Gardiner Julia L. Copas R.D. Elliott H.O.J. Collier 《Prostaglandins & other lipid mediators》1978,15(2):303-315
A novel test was developed to measure the tracheobronchial irritant activity of inhaled prostaglandins. Conscious restrained cats were challenged with seperate aerosols of PGE1, PGF2α, acetylcholine or isoprenaline. All of the aerosols except isoprenaline caused coughing in a concentration related manner. Tolerance developed very quickly to the tracheobronchial irritation and lasted 1–2 days for PGE1 and less than 1 day for PGF2α and acetylcholine. When a 3 day interval between each aerosol challenge was used, PGF2α was approximately 700 times more potent than acetylcholine as a tracheobronchial irritant. The highest PGE1 aerosol concentration (500 μg/ml) also caused sedation, diarrhoea and salivation. This test probably provides a useful method for evaluating the tracheobronchial irritant activity of potential prostaglandin bronchodilator analogues and for investigating the mechanism of action of prostaglandin induced tracheobronchial irritancy. 相似文献
11.
S.J. Konturek E.M. Miko R. Krl Z. Wierzbicki M. Dobrzaska 《Prostaglandins & other lipid mediators》1978,15(4):591-602
Previous studies of the effect of E series prostaglandins /PGs/ on insulin secretion gave conflicting results in animals and little information in man. This study was designed to determine the effect of methylated PGE2 analogue /15/S/-15-methyl PGE2 methyl ester/, given orally, intraduodenally or intravenously, on insulin secretion, both under basal conditions and in response to intraduodenal or intravenous administration of glucose in 22 male volunteers. Methylated PGE2 kept basal serum insulin level unchanged, but significantly reduced insulin response by 15 ± 6 μU/ml to intravenous glucose pulse injection /0.1 g/kg/ or by 45 ± 11 μU/ml to intraduodenal glucose infusion /0.5 g/kg-hr/. Blood glucose level was unaffected in tests with intraduodenal methylated PGE2, but in tests with intravenous administration it was significantly reduced. These studies demonstrate that methylated PGE2 analogue given orally, intraduodenally or intravenously results in a potent suppression of insulin response to glucose challenge. 相似文献
12.
Occurrence of Beauvericin and Enniatins in Wheat Affected by Fusarium avenaceum Head Blight
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We evaluated Fusarium contamination and the levels of hexadepsipeptide mycotoxins in 13 wheat samples affected by head blight in Finland. Fusarium avenaceum was the dominant species (91%) isolated from all samples, but isolates of F. culmorum (4%), F. tricinctum (3%), and F. poae (2%) also were recovered. Beauvericin (0.64 to 3.5 μg/g) was detected in all 13 samples. Enniatin B (trace to 4.8 μg/g) was detected in 12 samples, enniatin B1 (trace to 1.9 μg/g) was detected in 8 samples, and enniatin A1 (trace to 6.9 μg/g) was detected in 10 samples. Ten of 13 strains of F. avenaceum and 2 strains of F. poae and F. tricinctum produced beauvericin in culture on rice (trace to 70, 9.4, and 33 μg/g, respectively). All strains also produced enniatins (trace to 2,700 μg/g). This is the first report on the natural cooccurence of beauvericin and enniatins in wheat infected predominantly by F. avenaceum. 相似文献
13.
T-Cell-Line-Tropic Human Immunodeficiency Virus Type 1 That Is Made Resistant to Stromal Cell-Derived Factor 1α Contains Mutations in the Envelope gp120 but Does Not Show a Switch in Coreceptor Use
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Dominique Schols Jos A. Est Cecilia Cabrera Erik De Clercq 《Journal of virology》1998,72(5):4032-4037
The NL4.3 T-cell-line-tropic human immunodeficiency virus type 1 strain is sensitive to the CXC chemokine stromal cell-derived factor 1α (SDF-1α), the natural ligand for CXC chemokine receptor 4 (CXCR4); the 50% inhibitory concentration (IC50) in MT-4 cells is 130 ng/ml. We generated resistant virus through passaging of the virus in the presence of increasing concentrations of SDF-1α. After 24 passages, the virus was no longer sensitive to SDF-1α (SDF-1αres virus) (IC50, >2 μg/ml) and became resistant to SDF-1β (IC50, >2 μg/ml) and to a specific CXCR4 monoclonal antibody (IC50, >20 μg/ml). The SDF-1αres virus was about 10-fold less sensitive than the wild-type virus to the bicyclam AMD3100, a specific CXCR4 antagonist. The SDF-1αres virus contained the following mutations in the gp120 molecule: N106K in the V1 loop; S134N and F145L in the V2 loop; F245I in the C2 loop; K269E, Q278H, I288V, and N293D in the V3 loop; a deletion of 5 amino acids (FNSTW) at positions 364 to 368 in the V4 loop; and R378T in the CD4 binding domain. Replication of the NL4.3 wild-type virus and the SDF-1αres virus was demonstrated in U87 cells that coexpressed CD4 and CXCR4 (U87.CD4.CXCR4) but not in U87.CD4.CCR5 cells. Thus, the resistant virus was not able to switch to the CC chemokine receptor 5 (CCR5) coreceptor (the main coreceptor for macrophage-tropic viruses). The SDF-1αres virus replicated in HOS.CD4 cells expressing CCR1, CCR2b, CCR3, CCR4, CCR5, and CXCR4 but also in HOS.CD4.pBABE cells. However, all HOS transfectant cells expressed a low level of CXCR4. Neither of the two virus strains was able to infect HOS.CXCR4 or HOS.CCR5 transfectants, demonstrating the necessity of the CD4 receptor. The T-cell-line-tropic SDF-1αres virus was thus able to overcome the inhibitory effect of SDF-1α through mutations in gp120 but still needed CXCR4 to enter the cells. 相似文献
14.
Prostaglandin E2 (PGE2) applied cumulatively (1 nM − 1 μM) induced concentration-dependent tonic contractions in the longitudinal muscle of isolated rat rectum. The PGE2 effects were not altered by guanethidine (50 μM), whereas atropine (3 μM), guanethidine plus atropine or tetrodotoxin (0.1 μM) reduced them to an almost equal extent and increased the EC50 values for PGE2. The after-contractions following electrical stimulation were enhanced by PGE2 (10 nM) and inhibited by atropine. Diphloretin phosphate (DPP, 100 μM) shifted the regression lines for PGE2 to the right in both untreated and tetrodotoxin-treated preparations, and thereby increased the EC50 values. Slopes of the concentration-effect lines for PGE2 before and after DPP differed in the presence of tetrodotoxin. The regression line for PGE2 with SC 19220 (100 μM) in tetrodotoxin-treated preparations was shifted to the right in a parallel fashion. It is concluded that PGE2 exerted both a neural (cholinergic) and a smooth muscle effect. There may be a competitive antagonism between SC 19220 and PGE2 but the block by DPP may be nonselective. 相似文献
15.
The effects of prostaglandin E1 (PGE1) and indomethacin on isolated fetal and neonatal lamb mesenteric artery responses to norepinephrine were investigated. PGE1 (1.5μM) significantly reduced vasoconstriction responses to 0.5 to 5μM norepinephrine. Indomethacin (1μM) markedly potentiated the constrictor effects of 0.5 to 10μM norepinephrine. PGE1 prevented the potentiating effect of indomethacin. Neither PGE1 nor indomethacin altered basal muscle tension. These results suggest that endogenous PGs modify adrenergic responses in the isolated mesenteric arteries of preterm and newborn lambs. 相似文献
16.
Ming F. Tam Natalie W. Rice David H. Maillett Virgil Simplaceanu Nancy T. Ho Tsuey Chyi S. Tam Tong-Jian Shen Chien Ho 《The Journal of biological chemistry》2013,288(35):25512-25521
The E11 valine in the distal heme pocket of either the α- or β-subunit of human adult hemoglobin (Hb A) was replaced by leucine, isoleucine, or phenylalanine. Recombinant proteins were expressed in Escherichia coli and purified for structural and functional studies. 1H NMR spectra were obtained for the CO and deoxy forms of Hb A and the mutants. The mutations did not disturb the α1β2 interface in either form, whereas the H-bond between αHis-103 and βGln-131 in the α1β1 interfaces of the deoxy α-subunit mutants was weakened. Localized structural changes in the mutated heme pocket were detected for the CO form of recombinant Hb (rHb) (αV62F), rHb (βV67I), and rHb (βV67F) compared with Hb A. In the deoxy form the proximal histidyl residue in the β-subunit of rHb (βV67F) has been altered. Furthermore, the interactions between the porphyrin ring and heme pocket residues have been perturbed in rHb (αV62I), rHb (αV62F), and rHb (βV67F). Functionally, the oxygen binding affinity (P50), cooperativity (n50), and the alkaline Bohr Effect of the three α-subunit mutants and rHb (βV67L) are similar to those of Hb A. rHb (βV67I) and rHb (βV67F) exhibit low and high oxygen affinity, respectively. rHb (βV67F) has P50 values lower that those reported for rHb (αL29F), a B10 mutant studied previously in our laboratory (Wiltrout, M. E., Giovannelli, J. L., Simplaceanu, V., Lukin, J. A., Ho, N. T., and Ho, C. (2005) Biochemistry 44, 7207–7217). These E11 mutations do not slow down the autoxidation and azide-induced oxidation rates of the recombinant proteins. Results from this study provide new insights into the roles of E11 mutants in the structure-function relationship in hemoglobin. 相似文献
17.
Fumio Okada M.D. Tadaatsu Nukada M.D. Yoshihiro Yamauchi M.D. Hiroshi Abe M.D. 《Prostaglandins & other lipid mediators》1974,7(2):99-106
Intravenous administration of 50 μg of prostaglandin E1 (PGE1) induced a fall of the blood pressure in the patients with hypertension. It included essential, renal, renovascular hypertension and hypertensions associated with Takayasu's arteritis, primary aldosteronism, pheochromocytoma and anephric Kimmelstiel-Wilson syndrome. PGE1 at dose of 50 μg had little effect on the blood pressure in normotensives. The pattern and the degree of lowering blood pressure were not specific for each type of hypertension. The antihypertensive effect of PGE1 on essential hypertension was conspicuous in advanced cases.A clinical application of PGE1 to manage severe hypertension was discussed. 相似文献
18.
Prostaglandin E2 (PGE2) is induced in vivo by bacterial products including TLR agonists. To determine whether PGE2 is induced directly or via IL-1β, human monocytes and macrophages were cultured with LPS or with Pam3CSK4 in presence of caspase-1 inhibitor, ZVAD, or IL-1R antagonist, Kineret. TLR agonists induced PGE2 in macrophages exclusively via IL-1β-independent mechanisms. In contrast, ZVAD and Kineret reduced PGE2 production in LPS-treated (but not in Pam3CSK4-treated) monocytes, by 30–60%. Recombinant human IL-1β augmented COX-2 and mPGES-1 mRNA and PGE2 production in LPS-pretreated monocytes but not in un-primed or Pam3CSK4-primed monocytes. This difference was explained by the finding that LPS but not Pam3CSK4 induced phosphorylation of IRF3 in monocytes suggesting activation of the TRIF signaling pathway. Knocking down TRIF, TRAM, or IRF3 genes by siRNA inhibited IL-1β-induced COX-2 and mPGES-1 mRNA. Blocking of TLR4 endocytosis during LPS priming prevented the increase in PGE2 production by exogenous IL-1β. Our data showed that TLR2 agonists induce PGE2 in monocytes independently from IL-1β. In the case of TLR4, IL-1β augments PGE2 production in LPS-primed monocytes (but not in macrophages) through a mechanism that requires TLR4 internalization and activation of the TRIF/IRF3 pathway. These findings suggest a key role for blood monocytes in the rapid onset of fever in animals and humans exposed to bacterial products and some novel adjuvants. 相似文献
19.
R.A. Levine E.H. Schwartzel Jr. P.A. Randall S. Bachman 《Prostaglandins & other lipid mediators》1979,18(1):63-72
The action of prostaglandins and indomethacin on gastric mucosal cyclic nucleotide concentrations was evaluated in 18 anesthetized mongrel dogs. Prostaglandins E1 (PGE1) and E2 (PGE2) (25 μg/kg bolus, then 2 μg/kg/min) were administered both intravenously (4 experiments; femoral vein) and directly into the gastric mucosal circulation (10 experiments; superior mesenteric artery). The possible synergistic effect of pre-treatment and continuous arterial infusion of indomethacin (5 mg/kg bolus for 5 min, then 5 mg/min), a prostaglandin synthetase inhibitor, with PGE2 was studied in 4 experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. Doses of PGE1 and PGE2 which inhibited histamine-stimulated canine gastric acid secretion did not significantly alter antral or fundic mucosal cyclic nucleotide concentrations. Concomitant infusion of PGE2 with indomethacin did not potentiate the mucosal nucleotide response compared to PGE2 alone. These studies fail to implicate cyclic nucleotides as mediators of the inhibitory acid response induced by PGE1 or PGE2 in intact dog stomach. 相似文献
20.
Ventilatory tests (F.E.V.1/F.V.C.) have been studied in 16 asthmatic subjects during intermittent administration of corticotrophin, and the responses correlated with the plasma cortisol levels. The improvement in respiratory function was found to last for a longer period than the enhanced adrenocortical activity. 相似文献