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1.
The excitatory responses of neurones in the anterior cingulate cortex of the rat to iontophoretically applied substance P (SP) are reduced by noradrenaline (NA) applied iontophoretically or released from noradrenergic pathways. In order to determine the receptor involved in this inhibitory effect we have studied the effects of a number of receptor-specific adrenergic agonists and antagonists on responses of cingulate neurones to SP in rats anaesthetized with chloral hydrate. Low iontophoretic currents (0-15 nA) of NA, adrenaline and the beta-agonist, clenbuterol, all strongly reduced responses to SP. Isoprenaline was also effective but less consistently so, although problems were experienced with its iontophoretic release from micropipettes. The alpha 1-agonists, phenylephrine and methoxamine were also able to reduce responses to SP. However, this reduction required higher iontophoretic currents (15-60 nA) and was associated with depressant effects on baseline firing rate. The alpha 2-agonist clonidine was only weakly active at high currents and this too was associated with depression of baseline firing. Similar weak effects were noted with dopamine. The inhibitory effects of NA on SP responses were convincingly blocked or reversed by the beta-antagonist, practolol, but not by the alpha 1-antagonist, prazosin. The reduction of SP responses by phenylephrine was also blocked by practolol but unaffected by prazosin. Finally, reduction of SP excitations by activation of the coeruleocortical pathway was also blocked by practolol applied iontophoretically to the cortical cells. These results are consistent with the hypothesis that the effect of NA on SP responsiveness in the cingulate cortex is mediated by beta-adrenoreceptors. 相似文献
2.
Pharmaceutical Research - 相似文献
3.
H. Davidowa D. Albrecht H.-J. Gabriel S. Heublein K. Wetzel 《The European journal of neuroscience》1995,7(12):2364-2369
The effect of iontophoretically applied cholecystokinin (CCK) on neurons of the neostriatum was studied in rats anaesthetized with urethane. The most frequently observed effect of the sulphated octapeptide (CCK-8S) on striatal neurons was excitation. Spontaneously active neurons responded more often to CCK-8S than quiescent cells. Silent, primarily non-responsive neurons could often be stimulated with CCK-8S using glutamate to induce an ongoing discharge. Thus, 45.8% of the 177 neurons studied changed their discharge rate by more than 30%. Certain CCK receptor antagonists could prevent the effect of CCK-8S, fully or at least partly, in the majority of CCK-responsive neurons. The data suggest that cholecystokinin modulates the firing of active neostriatal neurons via the CCKA or the CCKB receptor type. Furthermore, we compared neuronal responses to glutamate with those recorded during concomitant administration of CCK-8S in order to study the interaction of both transmitters, which may be colocalized in striatal afferents. CCK-8S mainly enhanced the excitatory effect of glutamate on striatal neurons, but in several neurons the response to glutamate was reduced. The CCKB receptor antagonist could prevent CCK-8S from increasing the glutamate-induced activation. 相似文献
4.
Samples of human allograft skin prepared without freezing ("fresh skin) were found to have electrical and sodium ion transport properties which differed only slightly from those of skin which had been similarly treated but stored frozen (frozen skin). The fresh skin samples were less permeable to sodium ions during passive diffusion and less conductive than frozen skin at low current levels. They were more permselective for sodium versus chloride during constant-current iontophoresis and showed slightly more asymmetry in their current–voltage properties. Overall, the electrical behavior of the two tissues was similar enough to support the use of frozen tissue in iontophoresis studies. However, caution should be exercised when considering the use of frozen skin for applications, such as those based on electroosmosis, where the observed differences could have a major impact on the results. 相似文献
5.
Dr. P. D. Drummond 《Clinical autonomic research》1996,6(1):23-27
The presence of - and -adrenoceptors in the forehead microcirculation was investigated in 49 healthy subjects. Local vascular responses to noradrenaline, isoprenaline and adrenergic antagonists, administered transcutaneously by iontophoresis, were monitored via laser Doppler flowmetry. Iontophoresis of the -adrenergic antagonist phentolamine induced a persistent increase in skin blood flow, whereas iontophoresis of saline induced a minor increase in skin blood flow which subsided rapidly. Skin blood flow increased moderately after the iontophoresis of the -adrenergic antagonist propranolol. Pretreatment of the experimental site with phentolamine blocked the normal vasoconstrictor response to noradrenaline, and unmasked a minor vasodilator component of response in some subjects. Iontophoresis of the -adrenergic agonist isoprenaline induced dose-dependent vasodilatation which was antagonised by propranolol. These findings indicate that -adrenoceptors in the forehead microcirculation normally mediate a vasoconstrictor response to iontophoretically-applied noradrenaline. In addition, -adrenoceptors appear to mediate a minor vasodilator component of response. 相似文献
6.
Pharmaceutical Research - 相似文献
7.
Green Philip G. Hinz Robert S. Kim Aeri Szoka Francis C. Guy Richard H. 《Pharmaceutical research》1991,8(9):1121-1127
The iontophoresis of eight tripeptides, of the general structure alanine–X–alanine, has been measured across hairless mouse skin in vitro. The peptides were blocked (a) at the carboxyl terminus using the mixed anhydride reaction with t-butylamine and (b) at the amino terminus by acetylation with 14C-acetic anhydride. The nature of the central residue (X) was varied by selecting one of five neutral amino acids, two negatively chargeable moieties (aspartic and glutamic acids), and a positively chargeable species (histidine). Constant current iontophoresis at 0.36 mA/cm2, using Ag/AgCl electrodes, was performed for 24 hr in diffusion cells, which allowed both anode and cathode to be situated on the same (epidermal) side of a single piece of skin. Due to a combination of osmotic and electroosmotic forces, the anodal iontophoretic flux of neutral peptides was significantly greater than passive transport. Steady-state fluxes were not achieved, however, suggesting that time-dependent changes in the properties of the skin barrier may be occurring. Limited, further experiments confirmed that, on a 24-hr time scale, these changes were not fully reversible. The cathodal delivery of anionic permeants was well controlled at a steady and highly enhanced rate by the current flow. This behavior closely paralleled earlier work using simple negatively charged amino acids and N-acetylated amino acid derivatives. It appears that the normalized iontophoretic flux of these anionic species is independent of lipophilicity but may be inversely related to molecular weight. The positively charged peptide, Ac–Ala–His–Ala–NH(But), showed greater anodal iontophoretic enhancement when delivered from a donor solution at pH 4.0 than from a solution at pH 7.4. This was consistent with (a) the corresponding behavior of histidine alone and (b) the existence of a pK
a for these compounds at 6. Steady-state delivery was not achieved, although the levels of enhancement, especially at pH 4, were the largest observed. A preliminary investigation of tripeptide stability to either (i) electrolysis in the donor compartment or (ii) cutaneous metabolism revealed very little degradation under the conditions of the experiment. Overall, this research supports the principle of enhanced peptide delivery across the skin by iontophoresis and indicates a number of areas (e.g., mechanism and extent of current-induced changes in skin barrier function, molecular size dependence, pathways of current flow) on which further work should be focused. 相似文献
8.
Sensory Excitatory Postsynaptic Potentials Mediated by NMDA and non-NMDA Receptors in the Thalamus in vivo 总被引:4,自引:0,他引:4
Excitatory amino acid neurotransmitters, such as l-glutamate, act at several receptors in the brain, which are sometimes referred to as N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Extensive in vitro work indicates that both NMDA receptors and non-NMDA receptors contribute to excitatory postsynaptic potentials (epsps). The contribution of NMDA receptors to epsps in vivo under physiological conditions is, however, almost unknown. The receptors that mediate the epsps evoked in thalamic relay cells by natural stimulation of sensory afferents have been investigated in anaesthetized rats, and we report the first pharmacological characterization of an excitatory amino acid receptor-mediated epsp in vivo involving both non-NMDA receptors and, in particular, NMDA receptors. 相似文献
9.
目的 :观察中药离子导入治疗慢性前列腺炎的疗效 ,并评价它的安全性和可靠性。方法 :用自我专利技术“前列腺病离子治疗器直肠插入管”进行中药离子导入治疗已确定诊断的慢性前列腺炎患者共 3 6例 ,用主观症状改善率及前列腺液常规检查结果对比评估疗效。结果 :治疗组总有效率为 10 0 % ,痊愈率为 5 2 .8% ,副作用发生率为 13 .9% ,主观症状改善率与客观指标检测分析差别有显著性意义 (P <0 .0 0 1)。结论 :用自我专利技术“前列腺病离子治疗器直肠插入管”中药离子导入是治疗慢性前列腺炎的一种安全、有效的方法 相似文献
10.
The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm2 resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel and when combined with iontophoresis it was possible to deliver 10 mg/cm2/day of buspirone hydrochloride. 相似文献