INTERACTION BETWEEN EPIDERMAL GROWTH FACTOR AND ARGININE VASOPRESSIN IN RENAL MEDULLARY MEMBRANES

1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC₅₀ 2 ± 10^?7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.     

Cone dysfunction and supernormal scotopic electroretinogram with a high-intensity stimulus

An unusual form of scotopic electroretinogram with a bright white stimulus, which consisted of a rectangular a-wave of normal amplitude and a b-wave of supernormal amplitude, was recorded in three patients with cone dysfunction. In addition to poor visual acuity, abnormal color vision and reduced amplitude of the photopic electroretinogram, these patients showed a 2-log unit elevation of the dark-adaptation threshold. Funduscopic examination and fluorescein angiography revealed fine granular pigment disturbances at the mascula. The relationship between the response of the dark-adapted electroretinogram versus stimulus intensity was unique to these patients. The b-wave thresholds were elevated by 1 log unit. The b-waves were reduced in amplitude and markedly delayed in implicit time to dim stimuli, but supernormal in amplitude and normal in implicit time to bright stimuli.Abbreviations GMP guanosine monophosphate     

Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans

Summary The involvement of nitric oxide as an intracellular messenger in the control of insulin secretion from pancreatic Beta cells was studied in rat islets of Langerhans by measuring: (i) nitric oxide generation in response to physiological insulin secretagogues; (ii) the effects of inhibitors of nitric oxide synthesis on insulin secretory responses to physiological secretagogues, and on insulin synthesis; (iii) changes in islet cyclic guanosine monophosphate in response to secretagogues; (iv) the effects of exogenous cyclic guanosine monophosphate and dibutyryl cyclic guanosine monophosphate on insulin secretion from electrically permeabilised islets and from intact islets, respectively. These studies produced no evidence that nitric oxide generation is required for the initiation of insulin secretion by common secretagogues. However, the results of our experiments suggest that the generation of nitric oxide may be involved in long-term, glucose-dependent increases in cyclic guanosine monophosphate content of islet cells, although the physiological relevance of these changes requires further investigation.     

Pathophysiology of idiopathic dystonia: findings from genetic animal models

Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dt^sz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder.     

Effect of nitric oxide on mitogenesis and proliferation of cerebellar glial cells

In the brain, nitric oxide (NO) has been identified as a messenger molecule and a mediator of excitatory amino acid-induced neurotoxicity. In this study, the effects of NO on serum-induced mitogenesis and cell proliferation of the cerebellar glial cells were assessed. NO-generating agent, S-nitroso-N-acetylpenicillamine (SNAP) increased intracellular cyclic guanosine monophosphate (cGMP) levels. Furthermore, 2 chemically dissimilar NO-generating agents, SNAP and sodium nitroprusside (SNP) inhibited serum-induced thymidine incorporation and cell proliferation. The antimitogenic effect of NO was mimicked by 8-bromo-cGMP and blocked by hemoglobin, a known inhibitor of NO. The effect of NO was not cytotoxic, since the cells were not stained with Trypan blue and did not show increased release of lactate dehydrogenase in the culture supernatants. However, NO-treated cells showed decreased conversion of tetrazolium to blue formazan suggesting that NO inhibited mitochondrial activity in the glial cells. These results demonstrate that NO inhibits serum-induced mitogenesis and cell proliferation of cultured rat cerebellar glial cells.     

低剂量电离辐射对小鼠免疫器官cAMP和儿茶酚胺含量的影响

本文报道，７５ｍＧｙ／（１２．５ｍＧｙ／ｍｉｎ）单次全身Ｘ射线照射后９小时用ＳＲＢＣ免疫Ｃ５７ＢＬ／６小鼠，在免疫后４天和７天脾脏、胸腺和下丘脑ｃＡＭＰ含量均降低；而在免疫后４天脾脏去甲肾上腺素、肾上腺素和酪氨酸含量均增高，免疫后７天肾上腺素含量仍持续增高；当连接γ射线６５ｍＧｙ（０．０１５ｍＧｙ／ｍｉｎ，６ｈ／ｄ）全身照射小鼠后即刻或２９小时后免疫，脾脏和下丘脑ｃＡＭＰ含量也均降低。提示，低剂量     

受体导向单磷酸阿糖腺苷偶联物肝细胞导向性的实验研究

以乳糖化人血清白蛋白作为载体，与抗病毒药物单磷酸阿糖腺苷交联成导向抗病毒治疗药物（以下简称交联物），研究其对肝脏的导向性能。同位素标记示踪实验显示，交联物在肝脏内含量明显高于其它脏器（Ｐ＜０．００１）；用胶体金银染色法显示，受体定位于肝细胞血窦面及其侧面；交联物内化实验研究显示，其内化过程及动力学变化符合导向治疗要求。本研究为抗肝炎病毒导向治疗的临床应用提供实验依据。     

慢性低O2高CO2时NO-sGC-cGMP细胞信号转导通路变化及与肺动脉高压的关系

目的 :探讨慢性低O2 高CO2 性肺动脉高压发生与发展中NO sGC cGMP细胞信号转导通路的变化和作用。方法 :雄性Sprague Dawley大鼠随机分为对照组与低O2 高CO2 肺动脉高压 1w、2w及 4w组。用比色法测定血浆NO含量 ,酶动力学法测定肺组织sGC活性 ,12 5 I 放射免疫法检测肺组织cGMP含量。结果 :低O2 高CO2 1w、2w、4w组mPAP较对照组均明显升高 (P均 <0 .0 1)。而血浆NO含量、肺组织sGC活性和肺组织cGMP含量均显著降低 (分别P <0 .0 5,P <0 .0 1或P <0 .0 0 1)。mPAP与血浆NO含量 (r =-0 .80 7,P <0 .0 1)、与肺组织sGC活性 (r=-0 .754,P <0 .0 1)、与肺组织cGMP含量 (r=-0 .62 1,P <0 .0 1)之间均存在显著负相关。结论 :低O2 高CO2 引起的NO sGC cGMP转导通路的遏制性变化导致肺动脉舒张性降低是形成肺动脉高压的重要机制     

血管活性肠多肽对老龄勃起功能障碍大鼠的作用及机制研究

目的 观察血管活性肠多肽（VIP）对老龄勃起功能障碍（ED）大鼠的作用及其机制。方法40只SPF级雄性SD大鼠饲养至18月龄构建老龄模型大鼠,采用阿扑吗啡实验筛选老龄ED大鼠,阿扑吗啡实验结果阳性的老龄勃起功能正常大鼠为正常组,实验结果阴性的老龄ED大鼠为ED组和干预组,每组7只。干预组大鼠使用VIP 25 ng/kg隔日腹腔注射,治疗28 d。检测阴茎海绵体内压（ICP）及平均动脉压（MAP）评估勃起功能;酶联免疫吸附法检测大鼠阴茎海绵体组织环磷酸腺苷（cAMP）、一氧化氮（NO）含量;组织免疫荧光技术（IF）测大鼠阴茎海绵体组织血管性血友病因子（vWF）表达水平;蛋白质印迹法检测海绵体蛋白激酶A (PKA)、内皮源性一氧化氮合酶（eNOS）、血管性血友病因子（vWF）及血管内皮生长因子（VEGF）蛋白表达水平。结果 正常组、ED组和干预组基础ICP分别为（20.41±5.92）mmHg、（21.76±5.37）mmHg和（18.54±3.97）mmHg(1mmHg=0.133 kPa),MAP分别为（123.52±14.74）mmHg,(118.83±10.97)mmHg和（114...     

Ca2+ entry through the apical membrane reduces antidiuretic hormone-induced hydroosmotic response in toad urinary bladder

The role of Ca²⁺ in the regulation of antidiuretic hormone(ADH)-induced water permeability of the apical membrane of the toad urinary bladder was examined. The effects of modifying Ca²⁺ entry through the apical membrane of toad urinary bladders on the hydroosmotic water flow _H2O) and short circuit current (I _sc) were measured. In most experiments the bladders were treated with small amounts of Ag⁺ (10^–7 mol/l) on the apical side. This treatment was used because previous experiments indicate that it markedly increases alkali-earth cation fluxes through an amiloride-insensitive cation channel in the apical membrane of the urinary bladder. Moreover, when Ca²⁺ is the major cation in the apical solution of these Ag⁺-treated bladders, I _sc is mostly due to Ca²⁺ entry through the apical membrane. Ag⁺ increased I _sc and simultaneously inhibited _H2O in bladders perfused with Ca²⁺ solutions on the apical side. Addition of La³⁺ to the apical solution reversed the stimulation of I _sc and the inhibition of _H2O produced by Ag⁺. When bladders were perfused with Ca²⁺-free solutions on the apical side, addition of Ag⁺ did not inhibit _H2O while the stimulation of cation movements through the amiloride-insensitive cation channel persisted. In bladders perfused with apical Ca²⁺ solutions and treated with chlorophenyl thio-cyclic adenosine monophosphate (ClPheS-cAMP) the addition of Ag⁺ did not inhibit _H2O while it still increased I _sc. Finally, addition of Ca²⁺ to the apical solution of bladders not treated with Ag⁺ reduced _H2O. These results taken together with other findings in the literature suggest: (1) Ca²⁺ entry through the Ag⁺-treated amiloride-insensitive cation channel of the apical membrane inhibits _H2O; (2) the effects of Ca²⁺ entry are at a regulatory site that precedes the interaction of cAMP with the water channels; (3) it is also possible that Ca²⁺ entry through the unmodified amiloride-insensitive cation channel may have some inhibitory effect on _H2O.