共查询到20条相似文献,搜索用时 31 毫秒
1.
Gianfranco Delle Fave Anna Kohn Laura de Magistris Marcello Mancuso Claudio Sparvoli 《Life sciences》1980,27(11):993-999
The effect of bombesin on gastrin release and gastric acid secretion was investigated in 10 healthy volunteers. Bombesin (0.6 μg · Kg?1 · hr?1) produced a significantly higher increase in plasma gastrin levels (86.7 11.1 pmo/1 than after a protein meal (39.6 ± 5.6 pmol1/1). The gastric acid secretory response to bombesin (12.1 ± 2.9 mEq · hr?1) was however significantly lower than the maximal response produced by pentagostrin (20.9 ± 3.5 mEq · hr?1) at the dose of 6 μg · Kg?1. Atropine did not modify gastrin release induced by bombesin but significantly reduced gastric acid secretion . From the data presented it may be hypothesized that less biologically active forms of gastrin and/or other peptides inhibiting the gastrin effect upon gastric acid secretion may be released by bombesin. 相似文献
2.
The antiinflammatory activity of a homologous series of α-alkyl substituted [4-(1-oxo-2-iso-indolinyl)-phenyl]-acetic acid has been assayed by some and tests.These compounds were shown to be particularly active in inhibiting prostaglandin biosynthesis from bovine seminal vesicles, and their potency was seen to increase as the size of the substituents in the side chain increased.The antiinflammatory activity is not correlated with inhibition of PG-synthetase. Discussion of the data takes into account the plasma protein binding and pharmacokinetics of these compounds. 相似文献
3.
D Cunningham M Flashner S W Tanenbaum 《Biochemical and biophysical research communications》1979,86(1):173-179
Cytochalasin A (CA) at 5 × 10?5 strongly inhibits glucose transport in Arthrobacter sialophilis. This effect and other bacteriostatic and metabolic inhibitions of gram-positive bacteria are not caused by the closely related congeners cytochalasin B or D. Inhibitions by CA are nullified by prior drug incubation with sulfhydryl compounds. It was also found that the characterized adduct of CA with β-mercaptoethanol is devoid of biological activity. N-ethylmaleimide, p-chloromercuribenzoate and ethacrynic acid (a known, liposoluble, sulfhydryl reactant) were each shown at 5 × 10?5 to be relatively ineffective in inhibiting D-glucose transport in . These observations suggest that CA reacts at the molecular biological level in a site-specific manner. 相似文献
4.
Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines 总被引:45,自引:0,他引:45
Adenosine has a significant role in many functions of the central nervous system. Behaviorally, adenosine and adenosine analogs have marked depressant effects. Electrophysiologically, adenosine reduces spontaneous neuronal activity and inhibits transsynaptic potentials interaction with extracellular receptors. Biochemically, adenosine inhibits adenylate cyclase a “high” affinity receptor, and activates adenylate cyclase a “low” affinity receptor. These receptors, called “A1” and “A2” respectively, show differing profiles for activation by adenosine analogs. Radioactive N6-cyclohexyladenosine binds selectively to the “high” affinity receptor. One major class of antagonists is known at adenosine receptors: the alkylxanthines, including caffeine and theophylline. Radioactive 1,3-diethyl-8-phenylxanthine, a particularly potent antagonist, appears to bind to both low and high affinity adenosine receptors. Behavioral, electrophysiological, and biochemical effects of alkylxanthines are consistent with the hypothesis that the central stimulatory actions of caffeine and theophylline are due in large part to antagonism of central adenosine receptors. 相似文献
5.
Timothy S. Gaginella Thomas J. Rimele Thomas M. ODorisio Robert J. Dorff 《Life sciences》1980,26(19):1599-1608
Muscarinic receptors in the smooth muscle of the cat pylorus (pyloric sphincter) were identified by binding of the ligand (±) [3H]-quinuclidinyl benzilate ([3H]-QNB). Receptor related binding of [3H]-QNB reached steady-state in thirty minutes at 37°C, was saturable, showed pharmacologic specificity and was stereoselective. An apparent equilibrium dissociation constant, KD, of 1.9 ± 0.3 nM and maximum receptor concentration of 122 ± 13 femtomoles per mg of protein (means ± S.E.M.) were determined from Scatchard plots of [3H]-QNB binding. Hill coefficients of 0.99 and 1.01 indicated the absence of cooperative interactions. The muscarinic antagonists atropine and propantheline inhibited binding with IC50 values in the nanomolar range, whereas bethanechol was over four orders of magnitude less potent. Noncholinergic agents had little or no effect on [3H]-QNB binding. The isomer of QNB was about seventy times more effective at inhibiting binding than its isomer while benzetimide was greater than two thousand fold more active than benzetimide. The isomers of another anticholinergic compound, tropicamide, also competed for [3H]-QNB binding sites in a stereoselective manner, the isomer being eighty-five times more potent than the isomer. 相似文献
6.
A new steroid-like compound, Δ1-11-oxa-11-deoxycortisol, was tested in a one-week growth suppression, thymus suppression and adrenal weight suppression bioassay for possible glucocorticoid antagonist activity in . We hypothesized that this compound would have antiglucocorticoid activity based on previous studies of 11-deoxycortisol and Δ1,9(11)-11-deoxycortisol, which were optimal glucocorticoid antagonists in adrenalectomized rats, but which lost antiglucocorticoid activity in intact animals, apparently due to adrenal 11β-hydroxylation. Thus, Δ1-11-oxa-11-deoxycortisol, a compound which cannot undergo llβ-hydroxylation, was synthesized and tested as an antiglucocorticoid. This analog had an affinity for the rat thymus glucocorticoid receptor similar to that of its parent compounds (Ki 0.9-3.1×10?7M). A dose of 1 antagonized the effect of 15μg of dexamethasone in the growth suppression assay (p<0.05) and in the thymus suppression assay (p<0.06), but did not antagonize dexamethasone-induced adrenal weight suppression. Δ1-11-oxa-11-deoxycortisol did not exhibit glucocorticoid activity in any of the three assays. These data suggest that Δ1-11-oxa-11-deoxycortisol may be a pure competitive antagonist of dexamethasone. 相似文献
7.
Methods are described for purification of a vesicular membrane fraction of hog gastric mucosa using differential centrifugation, density gradient separation on zonal rotors and free-flow electrophoresis. As a result a fraction is obtained enriched 40-fold in terms of K+-ATPase and free of any other enzyme marker other than K+-activated phosphatase.the 5′-nucleotidase and basal Mg2+-ATPase are clearly separated from the latter enzymes.Osmotic shock, Triton X-100 treatment or K+ ionophores increased the K+-ATPase activity in isotonic conditions, but phosphatase is not affected by these treatments, nor is the ATPase activity in the presence of NH4+. The results suggest that the electrophoretic fraction contains a major population of tight vesicles, whose permeability to K+ is rate limiting for the ATPase activity but not for the phosphatase activity. It is concluded that K+ site for the ATPase is internal whereas the K+ site for the phosphatase is external, hence, the K+ site must be mobile across the membrane. 相似文献
8.
D Sarantakis W A McKinley N H Grant 《Biochemical and biophysical research communications》1973,55(2):538-542
The tetradecapeptide H-Ala-Gly-Ala-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Ala-OH (Ala3, 14-somatostatin) an analog of the somatotropin release inhibiting factor (somatostatin SRIF) was synthesized by solid phase peptide methods. It shows somatotropin release inhibiting activity at 5 μg/ml concentration. 相似文献
9.
The ability of a series of tetrahydroisoquinoline (THIQ) alkaloids to inhibit the binding of radioligands to catecholamine receptors in the CNS has been examined. THP was the most potent inhibitor of [3H] dihydroalprenolol binding to β-adrenergic receptors and of [3H] haloperidol to dopaminergic receptors and was the least potent inhibitor of [3H] WB-4101 binding to α-adrenergic receptors. Other THIQ alkaloids examined such as salsoline, salsolinol, and reticuline were less potent than THP in inhibiting radioligand binding to β-adrenergic and dopaminergic receptors, and more potent than THP in inhibiting radioligand to α-adrenergic receptors. The marked potency of THP in inhibiting radioligand binding to β-adrenergic receptors (IC50 ~ 10?7 M) was confirmed by the potency of this compound in inhibiting (?) isoproternol elicited accumulations of cyclic AMP in brain slice preparations. These data indicate that, if formed during alcohol consumption, THIQ derivatives such as THP may affect catecholamine neurons in the CNS. 相似文献
10.
The relative cardiovascular effects of trazodone and imipramine were compared in two open-chest, anesthetized dog models. Trazodone lowered arterial blood pressure (0.3 mg/kg), slowed heart rate (3 mg/kg) and reduced myocardial contractile force (3–10 mg/kg) following i.v. administration. Low i.v. doses (0.05–0.15 mg/kg) of imipramine increased arterial blood pressure and heart rate, presumably as a consequence of its known anticholinergic properties and/or effects on neuronal catecholamine re-uptake mechanisms. Subsequent to administration of 1.5 and 5 mg/kg, however, the vascular and myocardial depressant effects of imipramine were evident. Trazodone (1–10 mg/kg, i.v.), unlike imipramine, effected a substantial level of -adrenergic blockade a fixed challenge dose of norepinephrine, although less than that associated with phentolamine. Both trazodone and imipramine reduced aortic flow although different mechanisms. The reduction following administration of trazodone resulted from a decrease in heart rate whereas imipramine depressed aortic flow by lowering stroke volume. 相似文献
11.
W C Chen I J Sud D L Chou D S Feingold 《Biochemical and biophysical research communications》1977,74(2):480-487
The methyl ester hydrochlorides of amphotericin B and nystatin are less effective than the parent compounds in causing K+ release from human erythrocytes. The parent compounds and the derivatives are of comparable activity toward . The enhanced selective toxicity of polyene methyl ester salts for may mean that these antibiotics will be more effective therapeutic agents for systemic fungal infections. 相似文献
12.
The adenyl cyclase of the oxyntic, or acid-secreting, cells of bullfrog gastric mucosa has been found to be a membrane-bound enzyme. A method has been developed to isolate the adenyl cyclase rich membrane fractions in a hypotonic medium containing dithiothreitol, which has been found to protect the hormonal resposivenes of the adenyl cyclase.Highest specific activity of adenyl cyclase was localized in a light membrane fraction which also had abundant K+-stimulated ATPase and K+-stimulated phophatase and very low cytochrome oxidase activty. The three gastric secretagogues tested, namely histamine, pentagastrin and methylcholine, significantly stimulated the adenyl cyclase activity of the light membrane fraction.After treatment with 10 mM Mg+ further subfractionation of the light membrane fraction on a sucrose density gradient yielded light membrane subfraction 1, light membrane subfraction 2 and light membrane subfraction 3 in order of increasing densities. The three subfractions had different enzymatic and chemical properties. Adenyl cyclase activity has been found to be distributed in all three subfractions. However, the hormonal responsiveness of the three fractions was quite different. Light membrane subfraction 2 could be stimulated by all three secretagogues, light membrane subfraction 1 by histamine and methylcholine, while light membrane subfraction 3 was refractory to all three secretagogues. On the basis of the cholesterol to phospholipid molar ratio, RNA content, glycoprotein content and the enzymatic data it is suggested that light membrane subfraction 1 and light membrane subfraction 2 are of general plasma-membrane type, while light membrane subfraction 3 is largely of cytoplasmic origin. 相似文献
13.
Fluorescein isothiocyanate was used to covalently label the gastric (H+ + K+)-ATPase. FITC treatment of the enzyme inhibited the ATPase activity while largely sparing partial reactions such as the associated activity. ATP protected against inhibition suggesting the ligand binds at or near an ATP binding site. At 100% inhibition the stoichiometry of binding was 1.5 nmol FITC per mg Lowry protein a value corresponding to maximal phosphoenzyme formation. Binding occurred largely to a peptide of 6.2 isoelectric point, although minor labelling of a peptide of 5.6 was also noted. Fluorescence was quenched by K+, Rb+ and Tl+ in a dose-dependent manner, and the values of 0.28, 0.83 and 0.025 mM correspond rather well to the values required for dephosphorylation at a luminal site. Vanadate, a known inhibitor of the gastric ATPase produced a slow Mg2+-dependent fluorescent quench. Ca2+ reversed the K+-dependent loss of fluorescence and inhibited it when added prior to K+. This may relate to the slow phosphorylation in the presence of ATP found when Ca2+ was substituted for Mg2+ and the absence of K+-dependent dephosphorylation. The results with FITC-modified gastric ATPase provide evidence for a conformational change with K+ binding to the enzyme. 相似文献
14.
Yvette J. Fernandez Rose-Anne M. Boigegrain Claudie D. Cambon-Gros Salvador E. Mitjavila 《生物化学与生物物理学报:生物膜》1984,770(2):171-177
The aim of our work is to show the importance of the role of hydrophobic bonds in maintaining Mg2+-ATPase or sucrase activity and Na+-coupled d-glucose uptake normal for the brush border of rat enterocytes. The activity of the two enzymes and the d-glucose uptake were therefore measured under the action of and related to the fluidity determined by ESR. Three concentrations were used for the first eight alcohols, those of octanol being about 1500-times lower than those of methanol. For each alcohol the d-glucose uptake and the fluidity were linear functions of the logarithm of the concentration, the linear regressions being practically parallel and equidistant. The concentrations () of the eight alcohols inhibiting the d-glucose uptake by 80% were similar to those increasing the membrane fluidity by 3%. The linear relationship which existed in both cases between log 1 / and log being octanol / water partition coefficients of the alcohols, was evidence of great sensitivity to the hydrophobic effect of the alcohols. Only the first alcohols, however, produced any notable inhibition of Mg2+-ATPase and sucrase. Hydrophobic bonds are thus shown to have little influence in maintaining the activity of Mg2+-ATPase and sucrase, but they modulate the Na+-coupled d-glucose uptake. 相似文献
15.
Beatrice M. Anner 《Biochemical and biophysical research communications》1980,94(4):1233-1241
The effect of ATP on the kinetics of Na and K fluxes across the membranes of reconstituted sodium pump vesicles was examined. In the absence of ATP, the active vesicles equilibrated with 42K or 86Rb within 6 hours. In contrast, the equilibration of intravesicular Na with external 22Na was about 4 times slower. In the presence of ATP, the intravesicular K was replaced within 3 min by Na a Na:K exchange process. The total intravesicular Na pool was then labeled to the same specific radioactivity as the Na of the medium a Na:Na exchange process. The Na:K transport ratio varied with the intravesicular concentrations of Na and K. 相似文献
16.
Gastric microsomes do not contain any significant Ca2+-stimulated ATPase activity. Trypsinization of pig gastric microsomes in presence of ATP results in a significant (2–3-fold) increase in the basal (with Mg2+ as the only cation) ATPase activity, with virtual elimination of the K+-stimulated component. Such treatment causes unmaksing of a latent Mg2+-dependent Ca2+-stimulated ATPase. Other divalent cations such as Sr2+, Ba2+, Zn2+ and Mn2+ were found ineffective as a substitute for Ca2+. Moreover, those divalent cations acted as inhibitors of the Ca2+-stimulated ATPase activity. The pH optimum of the enzyme is around 6.8. The enzyme has a of 70 μM for ATP and the values for Mg2+ and Ca2+ are about and 10?7 M, respectively. Studies with inhibitors suggest the involvement of sulfhydryl and primary amino groups in the operation of the enzyme. Possible roles of the enzyme in gastric H+ transport have been discussed. 相似文献
17.
J Humphries T Wasiak Y P Wan K Folkers C Y Bowers 《Biochemical and biophysical research communications》1978,85(2):709-713
Ac-[Pro1, , -Trp3, -Trp6]-LH-RH completely inhibited ovulation in cycling rats at 200μg/rat and is comparable in activity to the corresponding D-1-analogue. This Ac-Pro1-analogue is the most potent antiovulatory peptide yet known having an -amino acid residue in position 1. This result shows that for the design of potent inhibitors of ovulation, a -amino acid residue is not essential in position 1. The corresponding Ac--Pro1- and Kic1-analogues completely inhibited ovulation at 750μg/rat, but not at 200μg/rat, and the Cpc1-analogue was inactive at these dosages. 相似文献
18.
Simultaneous intragastric administration of large doses of KCl (430 mg/kg and 860 mg/kg) with ethanol (4 g/kg) significantly reduces blood alcohol levels and diminishes manifestations of alcohol intoxication in rats. It was shown with parenteral administration of alcohol that the effect is not related to an acceleration of alcohol metabolism. Analysis of alcohol concentrations of gastric and intestinal content as well as studies with animals whose stomachs were ligated at the pylorus revealed that KCl interferes with the absorption of alcohol through inhibition of gastric absorption and gastric emptying. The finding that equimolal concentrations of NaCl were unable to duplicate the described effects characterizes them as specific actions of the potassium ion. 相似文献
19.