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排序方式: 共有305条查询结果,搜索用时 15 毫秒
1.
Ryo Suzuki M.D. Shunsaku Kobayashi 《Documenta ophthalmologica. Advances in ophthalmology》1988,70(4):293-300
Using tension-recording methods, we compared the effects of acetylcholine (Ach) and carbachol on the bovine iris sphincter. The isolated muscle strips were mounted in a 0.2 ml organ bath, through which Krebs solution at 36 °C flowed continuously. There was a tenthousandfold difference in potency between carbachol and Ach in this tissue. Neostigmine or eserine, acetylcholinesterase (AchE) inhibitors, produced a larger contraction of the muscle than did Ach. Ach-induced contractions were potentiated by low doses of anti-AchEs and were inhibited by atropine.This in vitro study suggests that Ach and/or endogenous chemical agents may be spontaneously released from tissues and that AchE activities in this tissue strongly inhibit or mask the Ach action, probably in order to protect the nerve terminals from released Ach. 相似文献
2.
Limatola Cristina Pacini Laura Candi Eleonora Spinedi Angelo 《Journal of neuro-oncology》1997,31(1-2):129-132
Stimulation of SK-N-BE(2) cells with 1 mM carbachol (Cch) elicited phosphoinositide (PPI) hydrolysis and a rapid elevation of cytosolic Ca2+ concentration ([Ca2+]i) from 115 nM to about 500 nM, followed by a plateau around 200 nM. In myo [3H]inositol-labelled cells, Cch-evoked accumulation of [3H]inositol phosphates (IPs) was not affected when [Ca2+]i was clamped at resting by cell loading with 10 M BAPTA/AM; under these conditions, maximal 1,4,5-inositol trisphosphate accumulation was not reduced either. When [Ca2+]i was clamped around 700 nM by cell treatment with 600 nM ionomycin, Cch-evoked [3H]IPs accumulation was enhanced by less than 20%, but it was impaired by a 30% and a 55% after [Ca2+]i reduction to about 70 nM and 35—50 nM, by cell loading with 20 M or 40 M BAPTA/AM, respectively. These results show that, in SK-N-BE(2) cells, Cch-activated PPI-specific phospholipase C is sensitive to [Ca2+]i but it already operates under suboptimal conditions at resting [Ca2+]i. 相似文献
3.
In their laboratory the authors have previously demonstrated that hippocampal slices could be induced to generate trains of "theta-like" oscillations by whole-bath perfusions of carbachol. Until recently, it has not been possible to generate similar activity in the septally deafferented hippocampus of an otherwise intact brain by microinfusions of carbachol. This study presents a full report of the first demonstration of a theta-like oscillation in the in vivo, septally deafferented hippocampal formation. Rats were anesthetized with urethane and implanted with microinfusion cannulae in the region of the medial septum/vertical limb of the diagonal band of Broca (MS/vDBB) and at single or multiple sites in the stratum moleculare of the fascia dentata. The MS/vDBB was microinfused with procaine hydrochloride to produce a reversible suppression lasting for approximately 20 minutes. Intrahippocampal microinfusions of carbachol or bicuculline alone (in the postprocaine condition of the MS/vDBB) failed to produce any theta-like oscillations. The combination of carbachol and bicuculline produced trains of theta-like oscillations during suppression of the MS/vDBB very similar to those seen in the slice preparations. The oscillations were blocked by intravenous administration of atropine sulfate, and they had the same depth profile as that of theta. Theta-on cells were shown to discharge in rhythmic bursts in synchrony with the oscillations. Thus, it would appear that the essential nature of the medial septal input to the hippocampal formation, for the generation of theta field activity in the intact brain, consists of a critical balance between cholinergic and GABAergic circuitry. 相似文献
4.
目的:比较氨甲酰胆碱和毛果芸香碱对血管内皮细胞M受体基因表达调节作用的异同点。方法:氨甲酰胆碱和毛果芸香碱分别孵育培养的牛主动脉内皮细胞10h后,提取细胞总RNA,RT-PCR方法测定M受体5个亚型mRNA的表达。结果:M_1~M_5受体mRNA在牛主动脉内皮细胞上均有表达,氨甲酰胆碱和毛果芸香碱孵育后表达量均增加,但二者之间无差异。结论:氨甲酰胆碱和毛果芸香碱对M受体5个亚型的基因表达均发生了相同的影响,两者对M受体可能的作用尚不能解释其对血管张力的影响。 相似文献
5.
Levetiracetam (LEV) is an approved drug for the treatment of some epileptic disorders. With few and controversial reports addressing its possible pharmacodynamic interactions, the current study aimed at studying the effect of LEV on isolated rat duodenal strips to enlighten its possible intestinal adverse effects using the isolated smooth muscle strips of rat duodenum. LEV showed a dose‐dependent inhibition in KCl (80 mm )‐induced contractions in normal Tyrode's solution. Moreover, preincubation with LEV (3 mm ) in K+‐rich/Ca2+‐free medium led to a significant decrease in the maximum contractions (Emax) coupled to a right shift of the cumulative CaCl2 concentration curves implying a possible Ca2+ channel blocking potential. In addition, LEV exhibited a typical noncompetitive inhibition in the cumulative carbachol concentration curves evidenced as a decrease in Emax without the alteration of EC50, thus eliminating any possible role of the muscarinic receptors in the relaxant effect. To rule out other possible relaxant mechanisms, tests were conveyed in Tyrode's solution containing either 100 μm l ‐NAME or 10 μm glimepiride to test the possible relaxant roles exhibited by nitric oxide (NO) and KATP channel opening, respectively. None of the tested pathways was involved in LEV‐mediated relaxation. Taken altogether, the results of the current study entail that LEV might exert a relaxant effect on intestinal smooth muscles through blocking L‐type voltage‐operated calcium channels, but not involving either NO release or KATP channel opening. 相似文献
6.
BACKGROUND: Interleukin 1beta (IL-1beta) is a potent inhibitor of gastric acid secretion. Regulatory actions at several levels have previously been demonstrated, including direct inhibition of parietal cell acid secretion. Although IL-1beta may activate several intracellular signalling pathways, the mechanisms responsible for inhibition of carbachol stimulated acid secretion have not been determined. AIMS: To investigate the roles of protein kinase C (PKC) and the sphingomyelinase signalling pathways in the regulation of acid secretion by IL-1beta. METHODS: Rabbit parietal cells were obtained by collagenase-EDTA digestion and centrifugal elutriation. Acid secretion stimulated by carbachol and A23187 (to mimic elevations in intracellular calcium) was assessed by 14C aminopyrine uptake in response to IL-1beta, PKC, and sphingomyelinase manipulation. RESULTS: IL-1beta inhibited carbachol and A23187 stimulated acid secretion in a dose dependent manner. The inhibitory actions were completely reversed by each of three different PKC inhibitors, staurosporine, H-7, and chelerythrine, as well as by PKC depletion with high dose phorbol ester pretreatment. IL-1beta did not downregulate parietal cell muscarinic receptor. IL-1beta significantly increased membrane PKC activity. Activation of the sphingomyelinase/ceramide pathway had no effect on basal or stimulated acid secretion. The inhibitory action of IL-1beta was independent of protein kinase A and protein kinase G activity. CONCLUSIONS: IL-1beta directly inhibits parietal cell carbachol stimulated acid secretion. This action occurs distal to muscarinic receptor activation and elevations in intracellular calcium and requires PKC. 相似文献
7.
8.
Joanne Heade Sam Maher Sinead B. Bleiel David J. Brayden 《Journal of pharmaceutical sciences》2018,107(6):1648-1655
In addition to their solubilizing properties, excipients used in lipid-based formulations can improve intestinal permeability of macromolecules. We determined whether admixing of medium-chain fatty acid (MCFA) permeation enhancers with a lipoidal excipient (Labrasol®) could potentiate transepithelial flux of a poorly permeable macromolecule (fluorescein isothiocyanate dextran 4 kDa [FD4]) across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of sodium caprate (C10), sodium undecylenate (C11:1), or sodium laurate (C12) combined with Labrasol® increased the apparent permeability coefficient (Papp) of FD4 to values typically seen with higher concentrations of MCFAs or Labrasol® alone. For example, combination of C11:1 (0.5 mg/mL) with Labrasol® (1 mg/mL) increased the Papp of FD4 by 10- and 11-fold over the respective individual agents at the same concentrations where no enhancement was evident. The increased enhancement ratios seen with the combinations were associated with some perturbation in intestinal histology and with attenuation of an epithelial functional measure, carbachol-stimulated inward short-circuit current. In conclusion, combining three MCFAs separately with Labrasol® increased the Papp of FD4 to values greater than those seen for MCFAs or Labrasol® alone. Ultimately, this may permit lower concentrations of MCFA to be used in combination with other excipients in oral formulations of poorly permeable molecules. 相似文献
9.
Timo KIRSCHSTEIN Chris PROTZEL Katrin PORATH Tina SELLMANN Rudiger KOHLING Oliver W HAKENBERG 《Acta pharmacologica Sinica》2014,35(1):74-81
Aim: Activation of muscarinic receptors on the detrusor smooth muscle is followed by contraction, which involves both myosin light chain kinase (MLCK) and Rho kinase (ROCK). The aim of this study was to determine the relative contributions of MLCK and ROCK to carbachol-induced contraction of human detrusor smooth muscle in vitro.
Methods: Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy. The strips were fixed in an organ bath, and carbachol or KCl-induced isometric contractions were measured by force transducers.
Results: Addition of carbachol (0.4-4 μmol/L) into the bath induced concentration-dependent contractions of detrusor specimens, which was completely abolished by atropine (1 μmol/L). Pre-incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK inhibitors HA1100 and Y-27632 (each at 10 μmol/L) significantly blocked carbachol-induced contractions as compared to the time-control experiments. Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol-induced contractions. The residual carbachol-induced contractions in the presence of both MLCK and ROCK inhibitors were significantly smaller than the contractions obtained when only one enzyme (either MLCK or ROCK) was inhibited, suggesting an additive effect of the two kinases. Interestingly, ROCK-mediated carbachol-induced contractions were positively correlated to the age of patients (r=0.52, P〈0.05).
Conclusion: Both MLCK and ROCK contribute to carbachol-induced contractions of human detrusor smooth muscle. ROCK inhibitors may be a new pharmacological approach to modulate human bladder hyperactivity. 相似文献
Methods: Detrusor smooth muscle strips were prepared from the macroscopically unaffected bladder wall of patients underwent cystectomy. The strips were fixed in an organ bath, and carbachol or KCl-induced isometric contractions were measured by force transducers.
Results: Addition of carbachol (0.4-4 μmol/L) into the bath induced concentration-dependent contractions of detrusor specimens, which was completely abolished by atropine (1 μmol/L). Pre-incubation of detrusor specimens with either the MLCK inhibitor ML-9 or the ROCK inhibitors HA1100 and Y-27632 (each at 10 μmol/L) significantly blocked carbachol-induced contractions as compared to the time-control experiments. Moreover, MLCK and ROCK inhibition were equally effective in reducing carbachol-induced contractions. The residual carbachol-induced contractions in the presence of both MLCK and ROCK inhibitors were significantly smaller than the contractions obtained when only one enzyme (either MLCK or ROCK) was inhibited, suggesting an additive effect of the two kinases. Interestingly, ROCK-mediated carbachol-induced contractions were positively correlated to the age of patients (r=0.52, P〈0.05).
Conclusion: Both MLCK and ROCK contribute to carbachol-induced contractions of human detrusor smooth muscle. ROCK inhibitors may be a new pharmacological approach to modulate human bladder hyperactivity. 相似文献
10.