影响氟哌啶醇治疗精神分裂症疗效因素的分析

为了进一步探讨影响氟哌啶醇（ＨＬ）治疗精神分裂症疗效的因素，对病程＜５年的３０例住院偏执型精神分裂症患者，以ＨＬ０．２０ｍｇｋｇ－１ｄ－１固定剂量治疗６周，以简明精神病评定量表、阳性症状评定量表、阴性症状评定量表（ＳＡＮＳ）评定疗效，以药物不良反应量表评定治疗副反应，放射免疫法测定药物浓度。结果：药物不良反应与临床疗效呈显著负相关，疗效好的患者游离氟哌啶醇血浆浓度反而较低。ＳＡＮＳ因子４（兴趣减少／社交活动减少）、因子５（注意障碍）的评分在治疗６周后比４周时有上升趋势。提示神经阻滞剂治疗造成的不良反应，会加重患者的某些阴性症状，最终导致总的临床疗效不满意。     

齐拉西酮合并氟哌啶醇治疗偏执型精神分裂症临床研究

目的:探讨齐拉西酮合并氟哌啶醇治疗偏执型精神分裂症的疗效及安全性. 方法:齐拉西酮合并小剂量氟哌啶醇治疗偏执型精神分裂症30例,采用阳性与阴性症状量表(PANSS)、治疗中出现的症状量表(TESS)评定疗效及不良反应,疗程6周. 结果:齐拉西酮合并小剂量氟哌啶醇治疗偏执型精神分裂症显效率86.7%,有效率96.7%,无明显锥体外系反应. 结论:齐拉西酮合并小剂量氟哌啶醇治疗偏执型精神分裂症疗效好,不良反应少.     

氯氮平与氟哌啶醇对血清一氧化氮含量的影响

目的：观察氯氮平与氟哌啶醇对精神分裂症患者血清一氧化氮(NO)含量的影响。方法：对122例精神分裂症患者随机分为氯氮平组和氟哌啶醇组，并分别再分为阳性症状为主(阳性组)和阴性症状为主(阴性组)。分别用氯氮平或氟哌啶醇治疗8周。治疗前和治疗第2、4、8周末分别检测血清NO含量，并观察各组之间NO动态变化。选择30名健康者为对照组。结果：治疗前血清NO含量两阳性组均显著高于正常对照组，两阴性组均显著低于正常对照组。两阳性组之间和两阴性组之间差异均无显著性；治疗后两阳性组血清NO含量均逐渐下降，到第8周末接近正常水平，与对照组相仿。而氯氮平组的阴性组逐渐上升，与治疗前比较，第4、8周末差异显著，第8周末与对照组相仿；氟哌啶醇组的阴性组逐渐上升，但与治疗前比较，到第8周末差异显著，与对照组比较差异仍显著。治疗后两阳性组差异无显著性；两阴性组，第2、4周末差异无显著性，第8周末有显著差异。结论：氯氮平和氟哌啶醇对精神分裂症患者血清NO含量有影响，阳性症状为主患者的血清NO含量降低，阴性症状为主患者血清NO含量升高，且氯氮平升高以阴性症状为主患者血清NO含量的作用较氟哌啶醇更为明显。     

自知力教育配合治疗精神分裂症对照研究

目的：探讨自知力教育在精神分裂症治疗中的作用。方法：对８２例精神分裂症患者随机分组,应用自知力教育配合氟哌啶醇（４０例）及单用氟哌啶醇（４２例）进行对照治疗,疗程１２周。采用简明精神病评定量表（ＢＰＲＳ）、阴性症状评定量表（ＳＡＮＳ）、阳性症状评定量表（ＳＡＰＳ）、及自知力与治疗态度问卷表（ＩＴＡＱ）进行测定。结果：自知力教育配合氟哌啶醇组疗效显著较好。结论：自知力教育配合治疗是治疗精神分裂症的有效方法,能较早、较好地出现治疗效果。     

氟哌啶醇治疗精神分裂症的增效作用

目的:评价奎硫平合并氟哌啶醇治疗精神分裂症的疗效与不良反应。方法:对110例单纯口服奎硫平的精神分裂症患者疗效不佳者合并氟哌啶醇治疗12周。用阳性症状和阴性症状量表(PANSS)评定疗效,用UKU不良反应评定量表评定不良反应。结果:治疗12周末PANSS量表总分及各分量表评分较治疗前均有显著下降(P<0.05或P<0.01);有效率达71.82%;不良反应无明显增加(P>0.05)。结论:奎硫平合并氟哌啶醇治疗精神分裂症疗效肯定,不良反应较轻。     

利培酮口服液合并氯硝西泮片治疗精神分裂症急性激越的对照研究

目的:比较利培酮口服液合并氯硝西泮片与氟哌啶醇肌内注射治疗精神分裂症急性激越症状的疗效及不良反应。方法:60例精神分裂症急性激越症状患者,按1:1比例随机分入利培酮口服液(2～6mg/d)合并氯硝西泮片(2～8mg/d)组(利培酮组)或氟哌啶醇肌注(5～20mg/d)组(氟哌啶醇组)治疗,疗程7d。采用阳性和阴性症状量表(PANSS)、阳性和阴性症状量表兴奋因子(PANSS-EC)、病人合作程度评定表、修改版外显攻击行为量表(MOAS)、临床疗效总体评定量表(CGI)评定疗效,采用治疗中出现的症状量表(TESS)、静坐不能评定量表(BAS)、锥体外系副反应量表(SAS),不良事件和实验室检查评定安全性。结果:在治疗7d后,利培酮组和氟哌啶醇组PANSS-EC评分分别为(11.1,3.6)分和(12.9,5.2)分,较治疗前均明显进步(P<0.01),两组间PANSS-EC和PANSS总分差异无统计学意义(P>0.05);利培酮组在阳性因子分、MOAS、合作程度改善方面均优于氟哌啶醇组(P<0.05);肌强直、静坐不能的发生率显著低于氟哌啶醇肌注组(P<0.01)。结论:利培酮口服液合并氯硝西泮片治疗精神分裂症急性激越症状与氟哌啶醇肌内注射疗效相当,在某些方面优于氟哌啶醇肌内注射。     

左旋咪唑涂布剂合并氟哌啶醇治疗精神分裂症的双盲对照研究

目的 探讨免疫增强剂－－左旋咪唑涂布剂合并氟哌啶醇治疗精神分裂症是否比单独应用氟哌啶醇效果更好。方法 将入组的精神分裂症患者分裂症患者机分为Ａ、Ｂ、Ｃ三组,每组均为３０例,Ａ组氟哌啶醇、自来水涂布。口服氟哌啶醇,左施咪唑涂布剂涂布,Ｃ组口服淀粉、左旋咪唑涂布剂涂布;进行为期十二周的治疗。应用简明精神病评定量表（）ＢＰＲＳ）、阳必 状评定量表（ＳＡＰＳ）、阴性症状谰定量表（ＳＡＮＳ）、临床疗效总评量     

阿立哌唑与氟哌啶醇治疗精神分裂症对照研究

目的:比较阿立哌唑与氟哌啶醇治疗精神分裂症的疗效和不良反应。方法:将116例精神分裂症患者随机平分为阿立哌唑组和氟哌啶醇组。疗程8周。采用阳性与阴性症状量表(PANSS)及副反应量表(TESS)在治疗前及治疗1、24、、8周末分别评定疗效和不良反应。结果:两组治疗后PANSS评分均显著减少(P<0.01)。治疗8周末阿立哌唑组减分率59.7%,阳性症状减分率67.9%,阴性症状减分率52.8%,有效率69.0%;氟哌啶醇组分别为41.3%,68.3%,4.1%和58.6%。不良反应阿立哌唑组少于氟哌啶醇组。结论:阿立哌唑治疗精神分裂症阳性症状疗效与氟哌啶醇相似,治疗阴性症状和一般精神病理症状优于氟哌啶醇,不良反应少,可作为治疗精神分裂症的一线用药。     

自知力教育配合氟哌啶醇治疗精神分裂症的疗效比较分析

目的　探讨自知力教育配合氟哌啶醇治疗精神分裂症的效果。方法　对 82例精神分裂症患者随机分为自知力教育配合氟哌啶醇组 (n =4 0 )及单用氟哌啶醇 (n =4 2 )治疗组 ,并进行比较分析。疗程 12周。采用简明精神病评定量表 (BPRS)、阴性症状评定量表 (SANS)、阳性症状评定量表 (SAPS)及自知力与治疗态度问卷表 (I TAQ)进行测定。结果　自知力教育配合氟哌啶醇组第 3周末ITSQ评分就较治疗前及氟哌啶醇组出现显著性差异 (P <0 .0 1) ;两组比较 ,自知力教育组的SAPS于第 9周末 ,BPRS及SANS于第 12周末总评分均出现差异性 (P<0 .0 1,P <0 .0 5 )。结论　自知力教育配合药物治疗是治疗精神分裂症的有效方法 ,能较早、较好地出现治疗效果。     

哌泊噻嗪、氟哌啶醇癸酸酯与氟奋乃静癸酸酯治疗精神分裂症的对照研究

建桐翁正【摘要】目的验证和比较哌泊噻嗪、氟哌啶醇癸酸酯、氟奋乃静癸酸酯三种长效抗精神病制剂对精神分裂症的疗效及副反应。方法采用多中心、开放随机对照研究，以简明精神病评定量表（ＢＰＲＳ）、阳性症状评定量表（ＳＡＰＳ）、阴性症状评定量表（ＳＡＮＳ）、临床疗效总评量表（ＣＧＩ）和副反应量表（ＴＥＳＳ）、锥体外系副反应量表（ＲＳＥＳＥ）综合评定。结果治疗后哌泊噻嗪组患者的ＣＧＩＳＩ与ＣＧＩＧＩ分值和ＳＡＮＳ量表总分均低于其它两组，差异均有显著性（Ｐ＜０．０５），而ＢＰＲＳ和ＳＡＰＳ量表总分治疗结束时三组间差异无显著性（Ｐ＞０．０５）。ＴＥＳＳ总分和ＲＳＥＳＥ总分在整个治疗过程中均以氟奋乃静癸酸酯组最高，哌泊噻嗪组最低。结论三组中以哌泊噻嗪对精神分裂症的疗效较好，对阴性症状的改善优于氟哌啶醇癸酸酯组和氟奋乃静癸酸酯组，对阳性症状的疗效近似。哌泊噻嗪组副反应较少，安全度较好     

GABA(B) receptor-mediated regulation of P2X7 receptor expression in the gerbil hippocampus

In the present study, the P(2)X(7) receptor expression in the gerbil hippocampus and GABA-mediated responses of its expression was investigated in order to identify the roles of the P(2)X(7) receptor on seizure activity and recovery mechanisms. P(2)X(7) receptor immunoreactivity in seizure-resistant (SR) gerbils was similar to that in pre-seizure group of seizure-sensitive (SS) gerbils. The administration of baclofen, a GABA(B) receptor agonist, P(2)X(7) receptor immunoreactivity was decreased in the mossy fiber, compared with that of non-treated gerbils, whereas treatment with phaclofen, a GABA(B) receptor antagonist, elevated P(2)X(7) receptor expression. Neither the treatments with GABA(A) receptor agonist nor antagonist affected P(2)X(7) receptor expression in the hippocampus. These findings suggest that altered P(2)X(7) receptor expression may not be involved in the epileptogenesis or seizure activity in gerbils, and presynaptic GABA(B) receptor-mediated actions may be closely related with the regulation of P(2)X(7) receptor expression in the gerbil hippocampus.     

Characterization of acetylcholinesterase and butyrylcholinesterase forms in normal and dystrophic Lama2dy mouse heart.

In searching for possible differences in acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) forms of dystrophic heart, the properties of ChE species in normal (NH) and dystrophic Lama2dy mouse heart (DH) were investigated. BuChE predominated over AChE. Loosely- and tightly-bound ChEs were released with saline (extract S1) and saline-Triton X-100 buffers (S2). About 50% of AChE, and 25% of BuChE, in NH or DH was measured in S1, and the rest in S2. Asymmetric AChE forms A12 (15%) and A8 (11%), globular hydrophilic G(H)4 (8%), amphiphilic G(A)4 (15%), and G(A)2+G(A)1 (51%) AChE species, and BuChE forms G(H)4 (13%), G(A)4 (3%), and G(A)2+G(A)1 (84%) were identified in NH and DH. Most of the asymmetric and G(A)4 AChE species were bound to Triticum vulgaris (WGA) or Ricinus communis (RCA) agglutinins. About half of G(H)4 and G(A)2+G(A)1 AChE were bound to WGA, and less (10%) to RCA. Variable amounts of G(H)4+G(A)4 (60%), and G(A)2+G(A)1 (75%) BuChE bound to WGA, and 50 and 10% to RCA. The lack of structural differences between ChE species in NH and DH indicates that, in contrast to the ChE forms in mouse skeletal muscle, the biosynthesis of ChE components in heart is not disturbed by dystrophy.     

Contribution of the combination of (201)Tl SPECT and (99m)T(c)O(4)(-) SPECT to the differential diagnosis of brain tumors and tumor-like lesions. A preliminary report

This study was undertaken to assess the contribution of the combination of (201)Tl SPECT and (99m)TcO(4)(-)SPECT to the differential diagnosis of brain tumors and tumor-like lesions. In the 8 patients selected for this study, both (201)Tl SPECT and (99m)TcO(4)(-) SPECT were performed because of clinical or radiological suspicion of brain tumor, no therapy was initiated before either SPECTs, diagnosis was based on biopsy, and MRI findings were stable in the interval between SPECTs. Histological diagnoses consisted of low grade glioma (n=1), high grade glioma (n=2), lymphoma (n=1), metastasis (n=1), multiple sclerosis (n=2) and cavernous angioma (n=1). Two high grade astrocytomas, one malignant lymphoma and one metastatic tumor showed (201)Tl accumulation and were diagnosed as tumor. The combination of (201)Tl and (99m)TcO(4)(-) did not change the diagnosis. One cavernous angioma showed no (201)Tl accumulation and was diagnosed as non-tumor. The combination of (201)Tl and (99m)TcO(4)(-) did not change the diagnosis. One low grade astrocytoma showed faint (201)Tl accumulation and was diagnosed as non-tumor. As (201)Tl uptake was higher than (99m)TcO(4)(-) uptake, the combination of (201)Tl and (99m)TcO(4)(-) changed the diagnosis to tumor. Two multiple sclerosis showed (201)Tl accumulation and were diagnosed as tumor. As (99m)TcO(4)(-) uptake was higher than (201)Tl uptake, the combination of (201)Tl and (99m)TcO(4)(-) changed the diagnosis to non-tumor. In three of the eight patients (38%), the combination of (201)Tl SPECT and (99m)TcO(4)(-) SPECT altered the diagnosis made by (201)Tl SPECT alone. In all of these three cases, the diagnosis made by the combination of (201)Tl SPECT and (99m)TcO(4)(-) SPECT was correct.     

m-Trifluoromethyl diphenyl diselenide attenuates glutaric acid-induced seizures and oxidative stress in rat pups: involvement of the γ-aminobutyric acidergic system

Glutaric acidemia type I (GA-I) is an inherited metabolic disease characterized by accumulation of glutaric acid (GA) and seizures. The intrastriatal GA administration in rats has been used as an animal model to mimic seizures presented by glutaric acidemic patients. m-Trifluoromethyl diphenyl diselenide, (m-CF(3) -C(6) H(4) Se)(2) , is an organoselenium compound that protects against seizures induced by pentylenetetrazole in mice. Thus, the aim of this study was to investigate whether (m-CF(3) -C(6) H(4) Se)(2) is effective against GA-induced seizures and oxidative stress in rat pups 21 days of age. Our findings demonstrate that (m-CF(3) -C(6) H(4) Se)(2) preadministration (50 mg/kg; p.o.) protected against the reduction in latency and the increased duration of GA (1.3 μmol/right striatum)-induced seizures in rat pups. In addition, (m-CF(3) -C(6) H(4) Se)(2) protected against the increase in reactive species generation and the reduction in antioxidant defenses glutathione peroxidase and glutathione S-transferase activities induced by GA. By contrast, no change in glutathione reductase or catalase activities was found. In addition, (m-CF(3) -C(6) H(4) Se)(2) was effective in protecting against inhibition of Na(+) ,K(+) -ATPase activity caused by GA in striatum of rat pups. This study showed for the first time that GA administration caused an increase in [(3) H]GABA uptake from striatum slices of rat pups and that (m-CF(3) -C(6) H(4) Se)(2) preadministration protected against this increase. A positive correlation between duration of seizures and [(3) H]GABA uptake levels was demonstrated. The results indicate that (m-CF(3) -C(6) H(4) Se)(2) protected against GA-induced seizures. Moreover, these findings suggest that the protection against oxidative stress, the inhibition of Na(+) ,K(+) -ATPase activity, and the increase in [(3) H]GABA uptake are possible mechanisms for the potential anticonvulsant action of (m-CF(3) -C(6) H(4) Se)(2).     

Abnormal neurogenesis in the dentate gyrus of adult mice lacking 1,25-dihydroxy vitamin D3 (1,25-(OH)2 D3)

In this study, we employed 1α-hydroxylase knockout (1α-(OH)ase(-/-) ) mice to investigate the influence of 1,25-dihydroxy vitamin D(3) (1,25-(OH)(2) D(3) ) deficiency on the adult neurogenesis in the hippocampal dentate gyrus (DG). The numbers of both 24-hr-old BrdU(+) cells and proliferating cell nuclear antigen positive cells in 8-week-old 1α-(OH)ase(-/-) mice increased approximately twofold compared with wild-type littermates. In contrast, the numbers of 7- and 28-day-old BrdU(+) cells in 1α-(OH)ase(-/-) mice decreased by 50% compared with wild-type mice, while the proportion of BrdU(+) /NeuN(+) cells in BrdU(+) population showed no difference between 1α-(OH)ase(-/-) and wild-type mice. Apoptotic cells in the subgranular zone (SGZ) of DG markedly increased in 1α-(OH)ase(-/-) mice. Replenishment of 1,25-(OH)(2) D(3) , but not correction of serum calcium and phosphorus levels, completely prevented changes in the neurogenesis in 1α-(OH)ase(-/-) mice. The absence of 1,25-(OH)(2) D(3) led to an increase in the expression of L-type voltage-gated calcium channel (L-VGCC) and a decrease in the nerve growth factor (NGF) mRNA level. Treatment with the L-VGCC inhibitor nifedipine blocked the increased cell proliferations by 1,25-(OH)(2) D(3) deficiency. Administration of NGF significantly attenuated the loss of newborn neurons in 1α-(OH)ase(-/-) mice.     

Cross-talking between 5-HT3 and GABAA receptors in cultured myenteric neurons

We recorded whole-cell ion currents induced by gamma-aminobutyric acid (I(GABA)) and serotonin (I(5-HT)) to investigate and characterize putative interactions between GABA(A) and 5-HT(3) receptors in myenteric neurons from the guinea pig small intestine. I(GABA) and I(5-HT) were inhibited by bicuculline and ondansetron, respectively. Currents induced by the simultaneous application of both, GABA and 5-HT (I(GABA+5-HT)) were significantly lower than the sum of I(GABA) and I(5-HT), indicating the existence of a current occlusion. Such an occlusion was observed when GABA(A) and 5-HT(3) receptors are virtually saturated. Kinetics, and pharmacological properties of I(GABA+5-HT) indicate that they are mediated by activation of both, GABA(A) and 5-HT(3) channels. GABA did not alter I(5-HT) in neurons without GABA(A) channels, in the presence of bicuculline (a GABA(A) receptor antagonist) or at the reversal potential for I(GABA). Similarly, 5-HT did not modify I(GABA) in neurons in which 5-HT(3) channels were absent, after inhibiting 5-HT(3) channels with ondansetron (a 5-HT(3) receptor antagonist) or at the reversal potential for I(5-HT). Current occlusion was observed as soon as GABA(A) and 5-HT(3) channels were being activated, in the absence of Ca(2+), at low temperature (11 degrees C), and after adding staurosporine (a protein kinase inhibitor) to the pipette solution. Our proposal is that GABA(A) and 5-HT(3) channels are organized in clusters and within these, both channels can cross-inhibit each other, likely by allosteric interactions between these proteins.     

Virol A, a toxic trans-polyacetylenic alcohol of Cicuta virosa, selectively inhibits the GABA-induced Cl(-) current in acutely dissociated rat hippocampal CA1 neurons

The effects of virol A (VA), a toxic component of Cicuta virosa (water hemlock), on the GABA-induced Cl(-) current (I(GABA)) in acutely dissociated rat hippocampal CA1 neurons were investigated using whole-cell patch-clamp techniques. VA reversibly reduced I(GABA) and the muscimol (Mus)-induced current (I(Mus)) in a concentration-dependent manner. The IC(50) values for VA against I(GABA) and I(Mus) were 9.6x10(-7) and 9.8x10(-7) M, respectively. VA shifted the EC(50) value of I(GABA) from 6.5x10(-6) to 2.1x10(-5) M, whereas it had no effect on the maximum response, thereby suggesting that VA inhibited I(GABA) in a competitive manner. VA had no apparent effect on current-voltage relationships for I(GABA), thus indicating the lack of voltage-dependency. On the other hand, application of VA (10(-6) M) did not additionally reduce the I(GABA) suppressed by >10(-5) M picrotoxin. VA but not bicuculline accelerated the decay phase of I(GABA), as was seen with picrotoxin. Moreover, pre-application of 10(-5) M VA reduced I(GABA). VA did not inhibit that induced by glycine (10(-4) M). These results indicate that VA inhibits I(GABA) by acting both on the GABA agonist site and on the Cl(-) channel of the GABA(A) receptor-channel complex. VA is a structurally novel type of compound that selectively inhibits the GABA(A) receptor-Cl(-) channel complexes in mammalian central nervous system neurons.     

Differential contribution of nitric oxide and cGMP to the stimulatory effects of growth hormone-releasing hormone and low-concentration somatostatin on growth hormone release from somatotrophs

There is increasing evidence that nitric oxide (NO) produced by NO synthase (NOS), and their signalling partners, guanylyl cyclase and cGMP, play a relevant role in growth hormone (GH) secretion from somatotrophs. We previously demonstrated that both GH-releasing hormone (GHRH; 10(-8) M) and low concentrations of somatostatin (10(-15) M) stimulate pig GH release in vitro, whereas a high somatostatin concentration (10(-7) M) inhibits GHRH-induced GH secretion. To ascertain the possible contribution of the NOS-NO and guanylyl cyclase-cGMP routes to these responses, cultures of pituitary cells from prepubertal female pigs were treated (30 min) with GHRH (10(-8) M) or somatostatin (10(-7) or 10(-15) M) in the absence or presence of activators or blockers of key steps of these signalling cascades, and GH release was measured. Two distinct activators of NO route, SNAP (5x10(-4) M) or L-AME (10(-3) M), similarly stimulated GH release when applied alone (with this effect being blocked by 10(-7) M somatostatin), but did not alter the stimulatory effect of GHRH or 10(-15) M somatostatin. Conversely, two NO pathway inhibitors, NAME (10(-5) M) or haemoglobin (20 microg/ml) similarly blocked GHRH- or 10(-15) M somatostatin-stimulated GH release. 8-Br-cGMP (10(-8) to 10(-4) M) strongly stimulated GH release, suggesting that cGMP may function as a subsequent step in the NO pathway in this system. Interestingly, 10(-7) M somatostatin did not inhibit the stimulatory effect of 8-Br-cGMP. Moreover, although 8-Br-cGMP did not modify the effect of GHRH, it enhanced GH release stimulated by 10(-15) M somatostatin. Accordingly, a specific guanylyl cyclase inhibitor, LY-83, 583 (10(-5) M) did not alter 10(-15) M somatostatin-induced GH release, whereas it blocked GHRH-induced GH secretion. These results demonstrate for the first time that the NOS/NO signalling pathway contributes critically to the stimulatory effects of both GHRH and low-concentration somatostatin on GH release, and that, conversely, the subsequent guanylyl cyclase/cGMP step only mediates GHRH- and not low-concentration somatostatin-induced GH secretion from somatotrophs.     

Effects of vasopressin and other neuropeptides on rostral medullary sympathoexcitatory neurons 'in vitro'

Neurons with intrinsic pacemaker activity and presumed sympathoexcitatory function were recorded in rat tissue slices within the confines of the rostroventrolateral reticular nucleus (RVL). These cells were excited in dose-dependent fashion by arginine vasopressin (AVP, 10(8)-10(6) M) but not by oxytocin (up to 10(7) M). The effect of AVP was mimicked by the V1-selective agonist [Phe2,Orn8]vasotocin (VT) (1 microM) but not by the V2-agonist [Val4,D-Arg8]vasopressin (VP) (1.9 microM). The effect of AVP (10(-7) M) was completely blocked by SKF 101926 (10(7) M), a non-selective antagonist and by d(CH2)5[Tyr(Me)2]AVP, a V1-selective antagonist but was unaffected by the V2-selective antagonist d(CH2)5[D-Ile2,Ile4,Ala-NH2 9]AVP. These cells were also activated by thyrotropin-releasing hormone (TRH) (10(-7)-10(-6) M), calcitonin gene-related peptide (CGRP) (4 X 10(-8) M), substance P, (10(-6) M), neuropeptide Y (NPY) (10(-8) M) and inhibited by Met-enkephalin (10(-6) M) and morphine (2 mM). Corticotropin-releasing factor (CRF) (10(-7) M) and angiotensin II (10(-6) M) were ineffective. In conclusion, RVL pacemaker neurons have vasopressin receptors reminiscent of the V1 (vascular and pressor) subtype. Their pacemaking activity is modulated by low doses of several other peptides also known to produce large vasomotor effects after introduction into the cerebroventricular space.     

Bradykinin-induced neuropeptide Y release by human pheochromocytoma tissue

Neuropeptide Y (NPY) and noradrenaline (NA) are frequently co-localized and co-released in the sympathetic nervous system. Since bradykinin (BK) is known to stimulate neurotransmitter release as NA in adrenal glands, we therefore hypothesized that BK might also be involved in the release of NPY. The effect of BK(1-9) on immunoreactive NPY (Ir-NPY) release was investigated in superfused human pheochromocytoma tissue. BK(1-9) (10(-7)-10(-5) M) was shown to induce a rapid Ir-NPY release in a concentration-dependent manner. This effect of BK(1-9) (10(-6) M) was mimicked by the B2 agonist [Phe(8)(CH(2)NH)Arg(9)]-bradykinin (10(-5) M) and blocked by the selective B2-receptor antagonist HOE140 (10(-5) M). Increasing Ir-NPY release was probably not mediated by nitric oxide (NO) since the outflow of Ir-NPY was not influenced by the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M). In presence of bapta-AM (10(-5) M), a chelator of cytosolic calcium, W7 (10(-5) M), a calmodulin inhibitor, TMB-8 (10(-5) M), a blocker of intracellular calcium mobilization and ryanodine (10(-5) M), a selective inhibitor of the Ca(2+)-induced release mechanism, the NPY release by BK(1-9) was significantly inhibited by 126%, 98%, 91%, and 94%, respectively. These results indicate that BK increased the release of NPY by the tumor acting through the interaction with the BK-B2 receptor and request intracellular calcium mobilization independently of a NO mechanism.