摘要:

A newly synthesized para-diphenylmethane derivative, N, N-dιethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), binds with high affinity to the microsomal anti-estrogen binding site (AEBS). Recent data suggest that the DPPE/AEBS binding site is closely related to a novel low-affinity, non-H1, non-H2 histamine site which may be associated with a calcium channel. We previously have shown that DPPE markedly reduces stress-induced and ethanol-induced gastric ulcers and attenuates gastric acid secretion. We now show that DPPE also profoundly reduces cysteamine-induced duodenal ulcers in rats

ISSN:0031-7012    

DOI:10.1159/000138477

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138478

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Using the charcoal meal test, the effects of morphine (3, 5 and 7 mg/kg) on gastrointestinal transit was assessed in normoglycemic as well as in acute and chronic hyperglycemic mice. Acute hyperglycemia was induced by intraperitoneal injection of glucose (5.04 g/kg), while chronic hyperglycemia was induced by streptozotocin injection (200 mg/kg i.p., 7–8 days before). Acute hyperglycemia augmented the inhibitory effect of morphine on gut transit, however, chronic hyperglycemia failed to modify the effects of morphine. The results indicate that hyperglycemia per se may not be the primary mechanism for the altered sensitivity to morphine in experimental models of diabete

ISSN:0031-7012    

DOI:10.1159/000138479

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In an experimental model of haemorrhagic shock that causes 100% mortality in rats within 30 min, the intravenous bolus injection (20 µg/kg) of sulfated cholecystokinin octapeptide (CCK-8) induces a prompt and sustained rise in blood pressure and pulse amplitude, all treated animals still surviving at the end of the experiment (2 h). This effect of CCK-8 is completely blocked by reserpine (5 mg/kg i.p.), significantly antagonized by prazosin (0.1 mg/kg i.v.) and yohimbine (1 mg/kg i.v.), and unaffected by practolol (15 mg/kg i.v.) and proglumide (0.2 mg/kg i.v.); it is completely antagonized by the intravenous (0.01–0.05 mg/kg), but not by the intracerebroventricular (0.002 mg/kg) injection of the ‘peripheral’ CCK antagonist, L-364,718. The present data indicate that the cardiovascular effects of CCK-8 in haemorrhagic shock involve peripheral CCK receptors, and require the functional integrity of the sympathetic nervous

ISSN:0031-7012    

DOI:10.1159/000138480

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The inhibitory effect of nitroglycerin (NG) on contractile responses to methoxamine (MO) and clonidine (CL) was investigated in isolated rabbit renal and femoral arteries. NG (10–7–10–5 mol/l) inhibited the responses to MO and CL in a noncompetitive manner and its inhibitory effect on CL-responses was much greater than that on the MO-responses. In the presence of phenoxybenzamine, however, NG (10–5 mol/l) markedly inhibited the residual response to MO. Contractile responses to KCl or added Ca2+ in a Ca2+-free medium containing KCl were slightly inhibited by NG. In the presence of nifedipine, NG (10–5 mol/l) markedly inhibited residual responses to CL but it only slightly inhibited the response to MO. In a Ca2+-free medium with EGTA, MO (10”5 mol/l) or CL (10–5 mol/l) induced a phasic contraction. NG had a greater inhibitory effect on the response to CL than MO. In a Ca2+-free medium with EGTA, nifedipine and MO (10–5 mol/l) or CL (10–5 mol/l), Ca2+ induced a tonic contraction. NG inhibited the Ca2+-response in the presence of CL, but it had little or no effect on the Ca2+-response in the presence of MO. These results suggest that in rabbit renal and femoral arteries, the potent inhibitory effect of NG on the responses to CL as compared to MO may be due to differences in the amount of receptor reserves that exist for both the agonists. In addition, the inhibition of voltage-dependent Ca2+ channels may not play a major role in the vasoinhibitory action of NG. Further, NG inhibits contractile responses due to mobilization of intracellular Ca2+ much more than the responses due to receptor-activated, nifedipine-insensitive Ca

ISSN:0031-7012    

DOI:10.1159/000138481

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The actions of many vasoactive drugs are mediated through, or modified by, the endothelium-derived relaxing (EDRF) and constricting (EDCF) factors. While EDRF appears to be nitric oxide, EDCF is a peptide or cyclooxygenase product. Using verapamil (a calcium channel blocker), propyl methylenedioxyindene (pr-MDI; an intracellular calcium antagonist), and sodium nitroprusside (which liberates nitric oxide from its molecular structure) as EDRF-independent pharmacological probes in rat aortic rings with and without endothelium, we attempted to provide additional insight into the role of extracellular ([Ca]o) and intracellular ([Ca]o calcium in EDRF and EDCF release and action, and to explain some mechanisms underlying the modulatory effects of these endothelial factors on the actions of vasoactive drugs. The findings suggest that (1) the [Ca]0 required for evoked EDRF release does not enter endothelial cells through verapamil-sensitive calcium channels; (2) mobilization of endoplasmic reticular [Ca]i by [Ca]0 entering the endothelial cell may be the trigger for evoked EDRF release; (3) spontaneous release of EDRF appears to depend more on mobilization of [Ca]i than on influx of [Ca]o; (4) the action of EDRF on smooth muscle either does not require Ca or does not involve the mobilization of [Ca]i by [Ca]0; (5) Both EDRF and EDCF can modulate the actions of vasoactive drugs; (6) the EDCF of the rat aorta is not a cyclooxygenase product, and (7) the action of EDCF on vascular smooth muscle, and possibly its release from endothelial cells, are Ca-dependent.

ISSN:0031-7012    

DOI:10.1159/000138482

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Self-sustained after-discharges (SSADs) induced by electric stimulation of the sensorimotor cortex in rats exhibited under control conditions a significant progressive prolongation with repeated stimulations. Clonazepam not only blocked this increase in duration but it suppressed and/or abolished SSADs in a dose-dependent manner. Clorazepate in the lowest dose used (10 mg/kg) did not change SSADs. The two higher doses (25 and 50 mg/kg) blocked the prolongation of the 4th SSAD, i.e. this effect had a relatively long latency.

ISSN:0031-7012    

DOI:10.1159/000138483

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Ten smokers participated in a study to compare the absorption of nicotine from the smoke aerosol of a new cigarette that heats, but does not burn tobacco (test) with a cigarette that burns tobacco (reference). The average plasma nicotine concentrations obtained by the 7th test cigarette (13 ng/ml) and 7th reference cigarette (24 ng/ml) were proportional to the nicotine yielded by the two cigarettes as determined under Federal Trade Commission machine-smoking conditions. These data demonstrate that the smoke aerosol obtained by smoking a cigarette which heats tobacco produces plasma profiles of nicotine that are similar to the profiles obtained from smoking a cigarette that burns tobacco.

ISSN:0031-7012    

DOI:10.1159/000138484

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The radiation exposure of human subjects is extrapolated from the elimination rate of radioactivity from the plasma and a single determination of the tissue distribution of radioactivity in rats. With an interval of 3–4 half-lives between administration and determination, the radiation exposure of an organ is underestimated only if the elimination rate from the organ is 5.5–12.9 times lower than from the plasma. Determining the elimination rate from the relevant organs is recommendable only if the radiation exposure calculated for the commonly used dose of 100 µCi per volunteer approaches the official yearly l

ISSN:0031-7012    

DOI:10.1159/000138485

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

A simple, economical method for the in vitro synthesis of milligram amounts of fluorescein monoglucuronide is presented. The compound can be synthesized in 1 day, and 2 chromatographic steps result in complete purification. The synthetic fluorescein monoglucuronide was found to be identical to biosynthetic fluorescein monoglucuronide by spectrophotometric and fluorometric criteria.

ISSN:0031-7012    

DOI:10.1159/000138486

出版商:S. Karger AG    

年代:1988

数据来源: Karger