摘要:

A new model of endotoxin (ET)-induced hyperalgesia has been used to test the effects of four classes of drugs in rats and mice. Hyperalgesia was assessed by paw pressure (PP), hot plate (HP) and tail flick (TF) tests. Each drug was injected intraperitoneally 24 and 12 h before ET injection and just before each pain test at 3, 6, 9 and 24 h after ET injection. At the dosages used, acetaminophen and dexamethasone were the most effective in reducing PP hyperalgesia and least effective on TF hyperalgesia, while indometacin and morphine produced their main effect on TF hyperalgesia. The four drugs were about equally effective in reversing HP hyperalgesia. We conclude that ET hyperalgesia is mediated by both prostaglandin-sensitive and prostaglandin-independent mechanisms.

ISSN:0031-7012    

DOI:10.1159/000139498

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The aim of the present study was to investigate the effect of nitric oxide (NO) synthase inhibition on gastric emptying rate in conscious rats and on gastric muscle contractility. The involvement of NO was also investigated in indometacin-induced (25 mg/kg, s.c.) changes in gastric emptying rate and smooth muscle contractility. L-NAME (NG-nitro-L-arginine methyl ester; 10 mg/kg, i.v.) inhibited the gastric emptying rate compared to controls and this effect was abolished by L-arginine (300 mg/kg, i.v.). Similarly, indometacin treatment led to a significant delay of gastric emptying rate with respect to vehicle-treated rats. Gastric longitudinal and circular muscle strips of L-NAME or indometacin-treated rats showed a reduction in contractile responses to carbachol. The results demonstrate that NO synthase blockade and indometacin treatment delay gastric emptying in conscious rats, concomitant with reduced responsiveness to carbachol, in vitro.

ISSN:0031-7012    

DOI:10.1159/000139499

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We examined the effects of histamine on mucin localized in the different regions and layers of rat gastric mucosa by determining the changes in the content as well as the biosynthetic activity of the mucin. In vivo administration of 0.8 mg/kg of histamine, which could not induce a concomitant gastric acid secretion, caused a significant increase in the mucin content in the corpus mucosa, but not in the antral mucosa. This increase was due to a significant accumulation of the mucin in the mucus gel and surface mucosa of the corpus region, whereas that in the deep mucosa did not significantly change. In the in vitro incubation system of rat gastric mucosa, histamine and dibutyryl cyclic AMP significantly increased [3H]-labeled mucin in the corpus. The histamine-induced acceleration of mucin biosynthesis was suppressed by ranitidine, but not pyrilamine. In the antrum, the biosynthetic activity showed no significant change by histamine. These results suggest that histamine promotes mucin metabolism via histamine H2 receptors in the surface mucosal layer of the corpus.

ISSN:0031-7012    

DOI:10.1159/000139500

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The effects of amitriptyline, a tricyclic antidepressant, on contractile responses to exogenously applied acetylcholine, endothelin 1 and high K+ were examined in the rat isolated trachea. Amitriptyline (0.3–30 µmol/l) produced a shift to the right of the logarithmic acetylcholine concentration-contraction curve without affecting the maximum contraction. Amitriptyline (10–100 µmol/l) significantly reduced the maximal contractile response to endothelin 1. The IC50 values were 10.3 and 30.2 µmol/l for inhibition of the submaximal contractile response to 1 mmol/l acetylcholine and to 50 nmol/l endothelin 1, respectively. Amitriptyline inhibited the high K+ (60 mmol/ l)-evoked contraction with an IC50 of 0.225 µmol/l. The inhibitory effect of amitriptyline was unchanged by the K+ channel blockers, charybdotoxin (100 nmol/l) and glibenclamide (up to 10 µmol/l). These results indicate that amitriptyline could antagonize the effect of acetylcholine and also exert direct inhibitory effect on muscle contraction of the rat trachea as a nonselective muscle

ISSN:0031-7012    

DOI:10.1159/000139501

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The pharmacokinetics of lamotrigine (LTG) and effects of carbamazepine (CBZ), valproic acid (VPA) and zonisamide (ZNS) on LTG kinetics were investigated in rats. LTG plasma levels were measured by high-performance liquid chromatography (HPLC). A single oral administration of LTG at 2.5–10 mg/kg showed linear disposition kinetics. In the pharmaco-kinetic parameters of LTG when combined with CBZ, the maximal plasma concentration (Cmax) and the area under the plasma concentration curve (AUC0–36) values were significantly lower and the time to maximal plasma concentration (Tmax) value was significantly higher than those in LTG alone. Furthermore, the Cmax and AUC0–36 values of LTG when pre-treated with CBZ for 7 days were significantly lower than those from simultaneous treatment with CBZ. The Cmax and AUC0–36 values of LTG when combined with VPA were significantly lower than those for LTG alone. There was no significant difference in the Tmax or time of elimination half-life (t½) values of LTG between simultaneous and pretreatment with VPA. Of the pharmacokinetic parameters of LTG with ZNS combination, the Cmax value of LTG after long-term dosings of ZNS decreased significantly, whereas no significant change in Cmax was observed after the combined single administration of LTG and ZNS. Single and chronic ZNS treatment did not significantly affect the Tmax, t½ and AUC0–36 values of LTG. The LTG trough level was significantly reduced by CBZ administration, reached the bottom level at 6 days after starting CBZ administration, and recovered gradually after withdrawal of CBZ. These results suggest that CBZ, VPA and ZNS causes changes in the plasma LTG level. They also suggest that in therapy combining LTG with one of these antiepileptics, especially CBZ, the LTG concentration in plasma should be monitore

ISSN:0031-7012    

DOI:10.1159/000139502

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Cadmium administered intraperitoneally at a dose of 1 mg/kg/day for 15 days caused a significant increase in mean arterial blood pressure. Endothelin-1 and noradrenaline produced concentration-dependent contractions of aortic rings that attained a lower maximal contraction in cadmium-injected rats as compared with control rats (p < 0.05). On the other hand, responses of aortic rings to different concentrations of potassium chloride did not show a significant difference between the groups. The decreased responsiveness of the aortae of cadmium-hypertensive rats to endothelin-1 and noradrenaline could either be due to an interaction of cadmium with receptors or intracellular signal transduction pathways of these agents, or it may simply reflect the adaptive changes in vascular tissues following hypertension development.

ISSN:0031-7012    

DOI:10.1159/000139503

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139504

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139505

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000139497

出版商:S. Karger AG    

年代:1997

数据来源: Karger