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1. |
Cytochemical Localization of the Acetone-lnducible Cytochrome P-450 Isoform, CYP2E1 in Murine Colonic Epithelium |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 339-347
Byung C. Park,
Ying Liu,
Damon R. Averill, Jr.,
Mary-Ione Jackman,
Daniel W. Rosenberg,
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摘要:
Immunolocalization of a toxicologically important cytochrome P-450 isoform, the alcohol-inducible CYP2E1, was examined in mouse colon. Male CD-1 mice (30–40 g) were exposed to acetone (1% v/v), a potent inducer of hepatic CYP2E1, in drinking water for 14 days. Tissue sections were fixed in 1% paraformaldehyde and incubated with anti-rat CYP2E1 polyclonal antibody. Immunohistochemical staining on tissue sections was performed using the indirect peroxidase-antiperoxidase method. In acetone-exposed mice, immunoreactivity was localized exclusively within the cytoplasm of surface epithelial cells of the proximal colon. Infrequently, only very faint staining was evident in colons of untreated control mice. Using the same monospecific antibody, the presence of CYP2E1 was confirmed by Western blot analysis. A 2- to 3-fold elevation in immunoreactivity corresponding to cytochrome P-4502E1 was found in colon microsomes isolated from acetone-exposed mice. Further evidence for colonic CYP2E1 is provided by elevation (up to 2.5-fold) in levels of chlorzoxazone 6-hydroxylase, a CYP2E1 substrate, after acetone treatment. The significance of these finding is discussed in terms of the potential for proximal colonic epithelial cells to participate directly in bioactivation of dietary promutagenic substance
ISSN:0031-7012
DOI:10.1159/000139302
出版商:S. Karger AG
年代:1995
数据来源: Karger
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2. |
Cytochrome P450Inhibitors Attenuate the Hypotonic Shock-Induced Increases in K+Efflux in LLC-PK1Cells |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 348-356
Ann Marie DelliPizzi,
John C. McGiff,
Bruno Escalante,
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摘要:
Cell volume regulation in LLC-PKi cells was evaluated by measuring 86Rb efflux (rate constant), used as an indicator of K+ efflux. Hypotonic shock induced a transient increase in the rate constant which returned to baseline values after 15 min. ETYA, an arachidonic acid-competitive antagonist as well as the cytochrome P450 inhibitors SKF 525-A, clotrimazole and 7-ethoxyresorufin, inhibited the hypotonic shock-induced increment in the rate constant. Arachidonic acid did not change hypotonic shock-induced increments in K+ efflux. LLC-PKi cells were unable to metabolize 14C-arachidonic acid. We concluded that although arachidonic acid inhibitors block the hypotonic shock-induced increment in K+ efflux, this effect cannot be related to inhibition of arachidonic acid metabolism.
ISSN:0031-7012
DOI:10.1159/000139303
出版商:S. Karger AG
年代:1995
数据来源: Karger
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3. |
MAO Inhibitors, Clorgyline and Lazabemide, Prevent Hydroxyl Radical Generation Caused by Brain Ischemia/Reperfusion in Mice |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 357-362
Tatsuya Suzuki,
Nobuhide Akaike,
Ken-ichi Ueno,
Yushiro Tanaka,
Norio Himori,
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摘要:
The effects of clorgyline, the MAO-A inhibitor, and lazabemide, the MAO-B inhibitor, on the levels of the hydroxyl radicals appearing in the cerebral ventricles of mice during brain ischemia/reperfusion were examined by using a salicylate trapping method. The amount of hydroxyl radicals formed peaked at 20 min after reperfusion (approximately 150% vs. basal level). The dopamine level markedly increased shortly after the initiation of an ischemic insult and thereafter waned. By contrast, the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) level decreased during a 40-min period of ischemia, gradually returning to the preischemic basal level upon reperfusion. The ischemia reperfusion-induced hydroxyl radical generation was attenuated by 3 mg/kg of clorgyline and lazabemide. Furthermore, mice pretreated with these MAO inhibitors showed decreased DOPAC levels in comparison with those of their respective vehicle-treated control groups; recovery of the reduced DOPAC level was also delayed. In conclusion, it is likely that both type A and type B MAOs participate in the generation of hydroxyl radicals during brain ischemia/reperfusion. This finding suggests the possible use of MAO inhibitors as neuroprotective agents for treating ischemic injury.
ISSN:0031-7012
DOI:10.1159/000139304
出版商:S. Karger AG
年代:1995
数据来源: Karger
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4. |
Suppression of Hypotensive Responses of Captopril and Enalapril by the Kallikrein Inhibitor Aprotinin in Spontaneously Hypertensive Rats |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 363-369
Jagdish N. Sharma,
Siti S. Amrah,
Abdul R. Noor,
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摘要:
The present investigation evaluated the effects of aprotinin, an inhibitor of kallikrein, on blood pressure responses, heart rate, and duration of hypotension induced by acute administration of captopril and enalapril (angiotensin-converting enzyme inhibitors) in anaesthetized spontaneously hypertensive rats. Captopril (20 mg/kg) and enalapril (20 mg/kg) administered intravenously caused a significant (p 0.05) to cause a fall in systolic and diastolic blood pressures in the presence of aprotinin (2 mg/kg). Captopril and enalapril were able to significantly reduce the heart rate (p < 0.05 and p < 0.001) in the presence as well as in the absence of aprotinin. The duration of hypotension produced by captopril and enalapril was abolished significantly (p < 0.001) in the presence of aprotinin. These findings may suggest that captopril and enalapril caused hypotension via the kallikrein pathway, since the kallikrein inhibitor aprotinin can antagonize the hypotensive responses of these agents. Thus, kallikrein may be an independent mediator in the regulation of blood pressure.
ISSN:0031-7012
DOI:10.1159/000139305
出版商:S. Karger AG
年代:1995
数据来源: Karger
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5. |
Characteristics of DQ2511 – Induced Relaxation in Isolated Dog, Monkey and Human Arteries |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 370-379
Tomio Okamura,
Shoichiro Ide,
Noboru Toda,
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摘要:
DQ2511, a possible antiulcer agent, relaxed dog, monkey and human arterial strips from various organs; the effect was most evident in the gastroepiploic artery. The relaxation was not influenced by timolol, atropine, dopamine receptor antagonists, and K+-channel blockers, but partially attenuated by oxyhemoglobin and endothelium denudation. Treatment with DQ2511 increased the relaxant response to sodium nitroprus-side and a prostaglandin I2 analog in dog gastroepiploic arteries and potentiated the stimulating effect of these agonists on the contents of cyclic GMP and cyclic AMP, respectively. It is concluded that DQ2511 relaxes gastroepiploic arteries predominantly over the other arteries; the relaxation appears to be derived partially from phosphodiesterase inhibition.
ISSN:0031-7012
DOI:10.1159/000139306
出版商:S. Karger AG
年代:1995
数据来源: Karger
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6. |
Vasodilator Effects of Liriodenine and Norushinsunine, Two Aporphine Alkaloids Isolated fromAnnona cherimolia,in Rat Aorta |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 380-387
S. Chuliá,
M.A. Noguera,
M.D. Ivorra,
D. Cortes,
M.P. D’Ocón,
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摘要:
The effect of two aporphines, liriodenine and norushinsunine, isolated from Annona cherimolia, were studied in the rat aorta in order to examine their mechanism of action. Both alkaloids (10–7–10–4 mol/l) showed relaxant effects on the contractions elicited by 10–6 mol/l noradrenaline (NA) or 80 mmol/l KC1, but, while liriodenine showed a nonspecific relaxant action on both spasmogens, norushinsunine was more potent on KC1-induced contraction. In Ca2+-free medium, both alkaloids (0.1 mmol/l) inhibited the responses elicited by NA, but not those elicited by caffeine. This inhibitory action occurred when the alkaloids were present during the release of the Ca2+ internal stores or during the refilling process. These results suggest that the two aporphines show a relaxant action in rat aorta which is mediated by an interaction with α1-adrenoceptors and an alteration of the Ca2+ entry via voltage-operated channels. Norushinsunine exhibits a certain degree of selectivity as an L-type Ca2+ channel
ISSN:0031-7012
DOI:10.1159/000139307
出版商:S. Karger AG
年代:1995
数据来源: Karger
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7. |
K-Channel Opening Activity of ZD6169 and Its Analogs: Effect on86Rb Efflux and3H-P1075 Binding in Bladder Smooth Muscle |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 388-397
Shephali Trivedi,
S.L. Stetz,
L. Potter-Lee,
M. McConville,
J.H. Li,
J. Empfield,
C.J. Ohnmacht,
K. Russell,
F.J. Brown,
D.A. Trainor,
S.T. Kau,
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摘要:
Zeneca ZD6169, (S,)-N--(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide, is a novel compound which relaxes urinary bladder smooth muscle in vitro. The effect of ZD6169 and two of its analogs on 86Rb efflux and 3H-P1075 binding in guinea pig bladder strips was investigated to characterize the K-channel opening properties of this compound. ZD6169 concentration dependently increased the rate of 86Rb efflux from guinea pig bladder strips. 86Rb efflux evoked by ZD6169 and its analogs was blocked by glibenclamide (30 µM) but not by charybdotoxin, apamin or α-dendrotoxin, suggesting that this compound activates KAtp channels in guinea pig bladder. In addition, interaction of ZD6169 with KAtp channels was also confirmed in human bladder smooth muscle cells. Specific binding of 3H-P1075, a potent opener of KAtp channels, to guinea pig urinary bladder strips was observed. 3H-P1075 binding was inhibited by known KAtp openers. ZD6169 inhibited binding of 3H-P1075 to urinary bladder strips like other structurally different KATp openers, e.g. cromakalim and pinacidil. Potencies for inhibition of 3H-P1075 binding by ZD6169 and other potassium channel openers correlate well with potencies for increase in 86Rb efflux and bladder muscle relaxation studies. It is concluded that Zeneca ZD6169 is a potassium channel opener which activates ATP-sensitive K-channels in guinea pig urinary bladder strips as well as in human bladder cells. Furthermore, binding studies suggest that the effects of ZD6169 and its analogs are mediated by binding to the site labeled by 3H-P1075 in guinea pig bladder strip
ISSN:0031-7012
DOI:10.1159/000139308
出版商:S. Karger AG
年代:1995
数据来源: Karger
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8. |
Author Index, Vol. 50, 1995 |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 398-399
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ISSN:0031-7012
DOI:10.1159/000139309
出版商:S. Karger AG
年代:1995
数据来源: Karger
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9. |
Subject Index, Vol. 50, 1995 |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page 400-404
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PDF (729KB)
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ISSN:0031-7012
DOI:10.1159/000139310
出版商:S. Karger AG
年代:1995
数据来源: Karger
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10. |
Contents, Vol. 50, 1995 |
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Pharmacology,
Volume 50,
Issue 6,
1995,
Page -
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PDF (690KB)
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ISSN:0031-7012
DOI:10.1159/000139301
出版商:S. Karger AG
年代:1995
数据来源: Karger
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