幼年大鼠皮质5—HT1A和5—HT2受体中介的膜电位变化

５－ＨＴ灌流幼年大鼠皮质脑片，２１．５％额叶后部ＩＶ层神经元出现慢超极化，膜电阻减小和ＥＰＳＰ抑制。此效应为５－ＨＴ１Ａ激动剂８－ＯＨ－ＤＰＡＴ模拟，为５－ＨＴ，拮抗剂ＮＡＮ－１９０阻抑，但ＥＰＳＰ抑制仍存在，超极化幅度随膜电位增大及胞外钾浓度增高而是减少，表明超极化由激活５－ＨＴ１Ａ受体导致钾外流增加所致，另有１１．８％神经元出现去极化伴膜电阻减小和ＥＰＳＰ抑制，５－ＨＴ２／５－ＨＴＩＣ拮抗剂Ｋ     

AVP_(4-8)增加海马组织内NGF mRNA和蛋白含量

本文采用了Ｎｏｒｔｈｅｒｎ杂交和ＥＬＩＳＡ法，观察了神经肽ＡＶＰ４－８对大鼠海马组织中神经生长因子（ＮＧＦ）ｍＲＮＡ和蛋白水平的影响，结果显示：给大鼠皮下注射ＡＶＰ４－８１２ｈ后，海马组织中ＮＧＦｍＲＮＡ的水平明显高于生理盐水对照组。而给大鼠皮下注射精氨酸加压素（ＡＶＰ）和催产素（ＯＴ）对ＮＧＦｍＲＮＡ的水平均无显著影响。另外，用ＡＶＰ４－８孵育离体大鼠海马组织切片，能使ＮＧＦ蛋白表达量升高，且在４．５ｈ左右达到高峰。     

侧脑室注射IL-1ra后脑缺血大鼠下丘脑室旁核CRH的表达

目的探讨白介素－１（ＩＬ－１）是否参与脑缺血大鼠下丘脑－垂体－肾上腺轴（ＨＰＡ）的激活。方法选用成年ＳＤ大鼠，分为１７组（Ａ～Ｑ组），Ａ组为正常对照组，Ｂ～Ｏ组大鼠脑缺血时间分别为１、３、６、２４、４８、７２ｈ及１、２、３、４、５、６、７、８周；Ｐ组的处理为：用微量注射泵将ＩＬ－１受体拮抗剂（ＩＬ－１ｒａ）注入大鼠侧脑室，之后建立脑缺血模型；Ｑ组为Ｐ组的对照组，用微量注射泵将生理盐水注入大鼠侧脑室，之后建立脑缺血模型。用免疫组化法显示各组大鼠下丘脑室旁核（ＰＶＮ）促肾上腺皮质激素释放激素（ＣＲＨ）的表达。结果正常大鼠ＰＶＮ有少量ＣＲＨ表达，脑缺血４８ｈ内ＰＶＮ无ＣＲＨ表达。从脑缺血７２ｈ起，ＰＶＮ之ＣＲＨ的表达开始增多，并且持续至脑缺血第８周。Ｐ组大鼠ＰＶＮ有较多ＣＲＨ表达，而Ｑ组大鼠ＰＶＮ无ＣＲＨ表达。结论ＩＬ－１可能通过促进下丘脑ＰＶＮ释放ＣＲＨ而参与脑缺血时下丘脑－垂体－肾上腺轴的激活。     

鱼肝油对急性期脑梗塞患者血清维生素A和细胞免疫水平的？…

目的 探讨鱼肝油对急性期脑梗塞患者血清维生素Ａ（ＶＡ）和细胞免疫水平的影响及他们之间的关系性。方法 用荧光分光光度法和碱性磷酸酶－抗碱性磷酸酶桥联酶标法（ＡＰＡＡＰ），测定血清ＶＡ和周围血Ｔ淋巴细胞亚群ＣＤ３、ＣＤ４、ＣＤ５。结果 治疗后血清ＶＡ水平较治疗前明显提高（Ｐ〈０．００１），ＣＤ３、ＣＤ４及ＣＤ４／ＣＤ８有提高趋势，治疗前后血清ＶＡ含量与ＣＤ３、ＣＤ４、ＣＤ４／ＣＤ８均呈显著正相关（Ｐ〈     

枕叶脑卒中视觉诱发电位与脑血流量相关性研究

对４６例枕叶脑卒中患者和４０例正常人进行视觉诱发电位（ＶＥＰ）检查，同时１３３Ｘｅ吸入法测定脑血流量。结果发现脑卒中组ＶＥＰ异常３１例（６７．４％）；对照组异常３例（７．５％），两组比较χ２＝２９．６，Ｐ＜０．０１。脑卒中组枕叶脑血流量平均４３．２±６．１ｍｌ．１００ｇ－１／ｍｉｎ，对照组４９．８±７．８ｍｌ．１００ｇ－１／ｍｉｎ，ｔ＝４．４，Ｐ＜０．０１。ＶＥＰ异常与枕叶脑血流量呈负相关，ｒ＝－０．３８７，Ｐ＜０．０１。伴有视野缺损ＶＥＰ异常率高。结果提示：ＶＥＰ对诊断视中枢损伤价值较大，尤其伴有视野缺损者意义尤大，ＶＥＰ异常与枕叶脑血流量呈负相关。     

鱼肝油对急性期脑梗塞患者血清维生素A和细胞免疫水平的影响及相关性研究

目的探讨鱼肝油对急性期脑梗塞患者血清维生素Ａ（ＶＡ）和细胞免疫水平的影响及他们之间的相关性。方法用荧光分光光度法和碱性磷酸酶—抗碱性磷酸酶桥联酶标法（ＡＰＡＡＰ），测定血清ＶＡ和周围血Ｔ淋巴细胞亚群ＣＤ３、ＣＤ４、ＣＤ８。结果治疗后血清ＶＡ水平较治疗前明显提高（Ｐ＜０．００１），ＣＤ３、ＣＤ４及ＣＤ４／ＣＤ８有提高趋势，治疗前后血清ＶＡ含量与ＣＤ３、ＣＤ４、ＣＤ４／ＣＤ８均呈显著正相关（Ｐ＜０．００５），治疗后血清ＶＡ含量与ＣＤ８水平呈显著负相关（Ｐ＜０．０５）。结论血清ＶＡ含量与机体免疫功能有关，鱼肝油能提高急性期脑梗塞患者血清ＶＡ水平和细胞免疫功能     

急性脑梗死患者血浆纤溶酶原激活剂抑制物活性及其启动子区 …

目的 探讨纤溶酶原激活剂抑制物（ＰＡＩ－１）活性和启动子基因多态性在急性脑梗死发病过程中的作用。方法 通过等位基因特异性寡核苷酸斑点要交技术，测定１０７例急性脑梗死患者和９５名健康人的白细胞ＰＡＩ－１启动子区４Ｇ／５Ｇ多态性位点的基因型，用发色底物法测定血浆ＰＡＩ－１活性。结果 脑梗死组血浆ＰＡＩ－１活性明显高于对照组，病例组和组织中４Ｇ／４Ｇ基因型患者的ＰＡＩ－１活性水平最高，４Ｇ／５Ｇ基因型次     

实验性局灶性脑血及再灌流后AP—1复合物的结合活性测定

本研究应用凝胶迁移法检测局灶脑缺血区中Ｆｏｓ与Ｊｕｎ基因的蛋白产物形成异源二聚体复合物－转录因子ＡＰ－（ａｃｔｉｖａｔｏｒ ｐｒｏｔｅｉｎ－１）的ＤＮＡ结合活性。缺血３０ｍｉｎ或９０ｍｉｎ伴随再灌流４ｈ，结果表明ＡＰ－１结合活性增加。提高的ＤＮＡ结合活性持续２４ｈ。以上结果说明提高转录因子ＡＰ－１的表达水平在缺血病变的基因调节改变中起一定作用。     

正常老人脑诱发电位研究：40例VEP和AEP分析

目的 为取得正常老人视觉诱发电位和听觉诱发电位有关资料及正常值。方法 应用丹麦Ｃｏｎｃｅｒｔｏ脑电仪及视觉、听觉刺激、对４０例正常老人的ＶＥＰ和ＡＥＰ作了检测。结果 ＶＥＰ和ＡＥＰ形态近似，提出Ｆｚ、Ｃｚ和Ｐｚ三脑区各指标的平均值，并对左右脑半球（Ｆ３－Ｆ４，Ｃ３－Ｃ４，Ｐ３－Ｐ４）作了比较。结论 正常老人ＶＥＰ和ＡＥＰ是较稳定的，本资料可作为今后研究老年精神病人ＶＥＰ和ＡＥＰ的基础。     

实验性癫痫时大鼠海马内兴奋性氨基酸受体对阿片肽含量的影响

应用免疫组织化学方法观察了青霉素致痫及海马内微量注射ＮＭＤＡ受体拮抗剂ＭＫ８０１（５－ｍｅｔｈｙ１－１０，１１－ｄｉｈｙｄｒｏ－５Ｈ－ｄｉｂｅｎｚｏ（ａ，ｄ）ｃｙｃｌｏｈｅｐｔａｎ－５，１０－ｉｍｉｎｅｍａｌｅａｔｅ）和非ＮＭＤＡ受体拮抗剂ＤＮＱＸ＊（６，７－ｄｉｎｉｔｒｏｑｕｉｎｏｘａｌｉｎｅ－２，３－ｄｉｏｎｅ）后，大鼠海马内吗啡肽Ａ１－１７和亮啡肽的含量变化，结果发现，在青霉素致痫４ｈ后，海     

Pharmacological characterization of a novel AVP(4-9) binding site in rat hippocampus

pGlu-Asn-Cys (Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)), a major metabolite C-terminal fragment of Arginine(8)-vasopressin (AVP), improves the disruption of the learning and memory, and is a far more potent in the mnemonic function than AVP. In this study, we pharmacologically characterized its putative binding site and mechanism of intracellular signaling. Radioligand binding assay showed that [35S]AVP(4-9) could detect specific binding sites in the rat hippocampus membrane preparations, and the binding site was specifically displaced by AVP(4-9) but not by either V(1) or V(2) antagonists. Furthermore, [35S]AVP(4-9) could not detect the cloned rat V(1a), V(1b) and V(2) vasopressin receptors. Even at a low doses (10-100 pM), AVP(4-9) caused an increase in both inositol(1,4, 5)-trisphosphate (Ins(1,4,5)P(3)) and intracellular calcium concentrations ([Ca(2+)](i)) in rat hippocampal cells. The AVP(4-9)-induced [Ca(2+)](i) increase was partially inhibited by the absence of Ca(2+) or by Ca(2+)-channel blocker, suggesting that AVP(4-9) caused the [Ca(2+)](i) increase via release from intracellular calcium store as well as influx from extracellular calcium. For the first time, this study provides evidence to show that AVP(4-9) activates Ins(1,4,5)P(3)/[Ca(2+)](i) pathway through a novel type of receptor in rat hippocampus, which might be potentially important in improving the mnemonic function.     

Anatomical and functional evidence for a role of arginine-vasopressin (AVP) in rat olfactory epithelium cells

The olfactory epithelium (OE) is composed of olfactory sensory neurons (OSNs) and sustentacular cells; it lies in the nasal cavity where it is protected by a thin mucus layer. The finely regulated composition of this mucus provides OSN with a suitable ionic environment. To maintain the functional integrity of the epithelium despite permanent physical, chemical and microbial aggressions, both OSNs and surrounding sustentacular cells are continuously renewed from globose basal cells. Moreover, the sense of smell is involved in so numerous behaviours (feeding, reproduction, etc.) that it has to cross-talk with the endocrine and neuroendocrine systems. Thus, besides its sensory function, the olfactory epithelium is thought to undergo a lot of complex regulatory processes. We therefore studied the effects of various neuropeptides on primary cultures of Sprague-Dawley rat olfactory epithelium cells. We found that arginine-vasopressin (AVP) triggered a robust, dose-dependent calcium increase in these cells. The cell response was essentially ascribed to the V1a AVP receptor, whose presence was confirmed by RT-PCR and immunolabelling. In the culture, V1a but not V1b receptors were present, mainly localized in neurons. In the epithelium, both subtypes were found differentially distributed. V1a-R were localized mainly in globose basal cells and at the apical side of the epithelium, in the area of the dendritic knobs of OSNs. V1b-R were strongly associated with Bowman's gland cells and globose basal cells. These localizations suggested potential multifaceted roles of a hormone, AVP, in the olfactory epithelium.     

Vasopressin(4-9) fragment activates V1a-type vasopressin receptor in rat supraoptic neurones.

The effect of vasopressin fragment 4-9 (AVP(4-9)) was investigated on freshly dissociated rat supraoptic neurones by measuring changes in intracellular calcium concentration ([Ca2+]i) using fura-2 microspectrofluorimetry. In 60% of neurones responding to vasopressin, AVP(4-9) induced a transient rise in [Ca2+]i that was dose-dependent in the concentration range 10 nM to 1 microM AVP(4-9) and strongly decreased in Ca2+-free buffer (84% inhibition). This [Ca2+]i response was completely and reversibly abolished by SR 49059 (1O nM), a specific V1a receptor antagonist, but not by SR 121463A, a specific V2 receptor antagonist. Our results demonstrate the presence of functional receptors activated by AVP(4-9) on vasopressin-sensitive neurones that possess the apparent pharmacological profile of the V1a-type vasopressin receptor.     

Effects of metabolic fragments of [Arg(8)]-vasopressin on nerve growth in cultured hippocampal neurons

The effects of metabolic fragments of [Arg(8)]-vasopressin (AVP), [pGlu(4), Cyt(6)]AVP (AVP(4-9)), and desglycinamide-[pGlu(4), Cyt(6)]AVP (AVP(4-8)) on the growth of hippocampal neurons in culture were investigated in comparison with those of AVP. AVP(4-9) caused a significant increase in filopodial length following 96 h of exposure at concentrations higher than 300 nM. AVP(4-9) was more potent than AVP. AVP(4-8) also induced an increase in filopodial length, but this effect was less than that of AVP. The selective V(1) agonist [Phe(2), Ile(3), Orn(8)]-vasopressin caused a significant increase in filopodial length, whereas the selective V(2) agonist [deamino-Cys(1), D-Arg(8)]-vasopressin showed no such effect. OPC-21268, a vasopressin V(1) antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V(2) antagonist OPC-31260 showed no such effect. A23187, a representative Ca ionophore, also increased filopodial length, and the A23187-induced increase in filopodial length was potentiated by AVP and AVP fragments. These results indicated that AVP(4-9) and AVP(4-8) increased filopodial length in cultured hippocampal neurons by activating V(1) receptors. Both phenomena induced by AVP(4-9) and AVP(4-8) were associated with intracellular calcium mobilization.     

AVP (4-8) improves concept learning in PFC-damaged but not hippocampal-damaged rats

A position reversal task was used to test the memory-enhancing effects of the arginine vasopressin analog [pGlu4, Cyt6] AVP (4-8) at a dose of 1.5 microg/kg. Rats received either sham operations (SHM), medial prefrontal cortex lesions (PFC), or hippocampal lesions (HIP). The peptide was administered daily, via s.c. injection, 30 min prior to training to half of the animals in each group. As expected, all animals performed equally well on the initial position habit and the first reversal. Overall, it was found that AVP (4-8)-treated animals performed significantly better across trials than saline (SAL)-treated animals. Further analysis showed that PFC animals that received AVP (4-8) (PFC+AVP) performed significantly better (at the level of controls) across trials than saline-treated PFC (PFC+SAL) animals. Sham animals that received the AVP (4-8) analog (SHM+AVP) only showed significant improvement on the last two reversals when compared to the sham saline-treated animals (SHM+SAL), which was likely due to a ceiling effect as performance reached high levels early in the reversal task. Trial 2 analysis across reversals revealed enhanced cognitive abilities in both sham groups (SHM+SAL, SHM+AVP) and the PFC+AVP group, but not in the PFC+SAL, HIP+AVP or the HIP+SAL groups. Hippocampal lesioned animals performed poorly on the task and injections of AVP (4-8) did not improve their performance. It is thus concluded that AVP (4-8) enhanced the acquisition of concept learning (win-stay/loose-shift) in this paradigm in PFC-damaged animals and ameliorated the perseverance habit that is often seen in PFC animals on this task. It is suggested that AVP (4-8) might have an enhancing effect on general cognitive abilities that is not limited to memory processes.     

Single unit response of suprachiasmatic neurons to arginine vasopressin (AVP) is mediated by a V1-like receptor in the hamster

A large population of local circuit neurons within the suprachiasmatic nucleus (SCN) exhibit immunopositive staining for arginine-vasopressin (AVP). AVP has been reported to be released from SCN neurons in a circadian pattern that peaks during the subjective day. Using an in vitro hypothalamic slice preparation, the present study investigated how SCN neurons respond to AVP over the circadian cycle and whether the response to AVP is mediated by V1- or V2-like AVP receptors. Exposure of the slice to AVP 10(-8) M produced excitatory responses in 51% of the 74 SCN neurons examined. A statistically significant day-night difference in the percentage of SCN units responding to AVP was observed (chi 2 = 15.62; P less than 0.01). During the dark phase 73% were excited by AVP, while during the light phase only 24% had excitatory responses. The threshold concentration of AVP ranged from 10(-9) to 10(-10) M and 10(-7) to 10(-8) M during the dark and light phase, respectively. In a second experiment the effects of selective V1 and V2 agonists and antagonists were determined. A V1, but not a V2 receptor antagonist was found to block the effects of AVP on single unit activity. Similarly, a V1 but not a V2 receptor agonist mimicked the effects of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for vasopressin V1 receptors of rostrodiencephalic neurons: Iontophoretic studies in the in vivo rat. Responses to oxytocin and to angiotensin

Extracellular recordings were obtained in anaesthetized rats from single neurons located in various structures around the rostral end of the third ventricle, known to harbour integrative neurons sensing deficiencies in and originating corrective responses for water-electrolyte balance. Once arginine vasopressin (AVP) responsive neurons were located, a selective antidiuretic agonist (binding to V2 receptors) and either V1 (presser response related) or V2 (antidiuretic) antagonists were iontophoretically applied. Neurons in this region did not respond to the V2 agonist and only the VI antagonist was able to block the response to AVP. It is assessed that the investigated region has neurons equipped only with receptors of the VI type. Interestingly, a number of these neurons also responded to angiotensin II (All), oxytocin and to blood pressure changes. The integrative neuronal population of parasagittal rostrodiencephalic neurons seem therefore to sense indices of haemodynamic changes including their neuro-hormonal signals within the brain such as All and AVP which bind to V1 (pressor response related) receptors.     

Influence of arginine vasopressin receptors and angiotensin receptor subtypes on the water intake and arterial blood pressure induced by vasopressin injected into the lateral septal area of the rat

In this study we investigated the influence of d(CH2)5-Tyr(Me)-[Arg8]vasopressin (AAVP) and [adamanteanacetyl1,0-ET-d-Tyr2,Val4,aminobutyryl6,Arg8,9]-[Arg8]vasopressin (ATAVP), which are antagonists of vasopressin V1 and V2 receptors, and the effects of losartan, a selective angiotensin AT1 receptor antagonist, and CGP42112A, a selective AT2 receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg8]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT1 and AT2 ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT1 receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V1 receptors and that the inhibitory effect requires V2 receptors. The involvement of AT1 and AT2 receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance.     

Localization and pharmacological characterization of high affinity binding sites for vasopressin and oxytocin in the rat brain by light microscopic autoradiography

Sites which bind tritiated vasopressin (AVP) with high affinity were detected in the brain of male, adult rats, by light microscopic autoradiography. Their anatomical localization differed markedly from that of high affinity binding sites for tritiated oxytocin (OT) determined in the same animal. Co-labelling was minimized by using low concentrations of [3H]AVP and [3H]OT. Binding of the former occurred predominantly in several structures of the limbic system (septum, amygdala, bed nucleus of the stria terminalis, accumbens nucleus), in two hypothalamic nuclei (suprachiasmatic and dorsal tuber) and in the area of the nucleus of the solitary tract. Binding of OT was evidenced in the olfactory tubercle, the ventromedial hypothalamic nucleus, the central amygdaloid nucleus and the ventral hippocampus. The ligand specificity of the binding sites was assessed in competition experiments. Synthetic structural analogues were used, allowing to discriminate OT receptors (OH[Thr4,Gly7]OT) from V2 receptors (dDAVP and d[Tyr(Me)2]VDAVP), V1 receptors ([Phe2,Orn8]VT) and V1b receptors (desGly9d(CH2)5AVP). Our main conclusions are, firstly, that AVP and OT binding sites can be readily distinguished, and that there is virtually no overlap in their distribution in the rat brain. Second, we showed that the sites which bind AVP with high affinity in the brain are V1 receptors, different both from the renal V2 receptors and from the anterior pituitary V1b receptors. Our results support the conjecture that AVP and OT play a role in interneuronal communication in the brain.     

Role of arginine vasopressin V1 and V2 receptors for brain damage after transient focal cerebral ischemia.

Brain edema formation is one of the most important mechanisms responsible for brain damage after ischemic stroke. Despite considerable efforts, no specific therapy is available yet. Arginine vasopressin (AVP) regulates cerebral water homeostasis and has been involved in brain edema formation. In the current study, we investigated the role of AVP V1 and V2 receptors on brain damage, brain edema formation, and functional outcome after transient focal cerebral ischemia, a condition comparable with that of stroke patients undergoing thrombolysis. C57/BL6 mice were subjected to 60-min middle cerebral artery occlusion (MCAO) followed by 23 h of reperfusion. Five minutes after MCAO, 100 or 500 ng of [deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-vasopressin (AVP V1 receptor antagonist) or [adamantaneacetyl(1), O-Et-D-Tyr(2), Val(4), Abu(6), Arg(8,9)]-vasopressin (AVP V2 receptor antagonist) were injected into the left ventricle. Inhibition of AVP V1 receptors reduced infarct volume in a dose-dependent manner by 54% and 70% (to 29+/-13 and 19+/-10 mm3 versus 63+/-17 mm3 in controls; P<0.001), brain edema formation by 67% (to 80.4%+/-1.0% versus 82.7%+/-1.2% in controls; P<0.001), blood-brain barrier disruption by 75% (P<0.001), and functional deficits 24 h after ischemia, while V2 receptor inhibition had no effect. The current findings indicate that AVP V1 but not V2 receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. Although further studies are needed to clarify the mechanisms of neuroprotection, AVP V1 receptors seem to be promising targets for the treatment of ischemic stroke.