The effects of A 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635

The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT_1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin (TTX), 60 mM K⁺ and perfusion with Ca²⁺-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT_1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT_1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT_1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT_1A receptors. Received: 11 September 1996 / Accepted: 25 November 1996     

大鼠食管颈段神经形态的组化研究

本文采用多种组化方法结合神经银染技术,对大鼠的食管颈段神经形态观察发现:延髓内双侧疑核的咀侧端及迷走神经背核闩平而附近,分别见散在的多极和梭形标记细胞;颈前、中节、颈胸节和胸交感节(T_2-T_4),结状节,脊神经节(C_2-C_8)内均见标记细胞。 食管壁内的神经束及分支,由粗、细两类神经纤维组成。其中AchE阳性的胆碱能纤维占优势,分别见于外膜丛、肌内丛、粘膜下丛,腺体血管周围和粘膜肌内,粗纤维末梢伸向上皮基部和上皮之间,肌内的神经末梢呈结状膨大。外膜和肌肉见有神经节和散在的神经细胞。而食管壁内肾上腺素能纤维稀少,仅见于神经束和分支内及血管壁周围。     

Effects of epidermal growth factor in the mammalian central nervous system: Its possible implications in brain pathologies and therapeutic applications

The development and maintenance of the normal functional integrity of the mammalian central nervous system is under the influence of a number of growth and trophic factors. One such growth factor, epidermal growth factor, has been detected in the mammalian brain and found to be associated with various brain regions and cell types. This small ubiquitous polypeptide can influence the proliferation, Metabolism, and differentiation of both glia and neurons in the central nervous system. We discuss the effects of epidermal growth factor on glial and neuronal cell function in an attempt to understand its role in development and maintenance of normal brain integrity. In addition, we review its possible implications in several pathological states in the central nervous system and speculate on therapeutic applications for this growth factor. © 1992 Wiley-Liss, Inc.     

Decreased [H]hemicholinium binding to high-affinity choline uptake sites in aged rat brain

The binding of [³H]hemicholinium ([³H]HCh-3) to sodium-dependent high-affinity choline uptake sites provides a useful neuroanatomical and functional marker of the cholinergic system. We examined the autoradiographic distribution of [³H]HCh-3 binding sites in the forebrain of young (4–6 months) and old (32 months) rats. There was a widespread reduction of [³H]HCh-3 binding site density in the aged rat brain. This loss presented regional differences with maximal reduction in the medial and posterior striatum (55%) and in the dentate gyrus (47%), in limbic areas such as basolateral amygdala, tubercle olfactorium and piriform cortex the autoradiographic signal was about 25–30% lower. In aged hippocampus and cerebral cortex the density of [³H]HCh-3 binding sites was about 40% lower, the difference between young and senescent animals being less evident in the medial septum and basal nucleus. No significant alterations were observed in interpeduncular nucleus from old rats. These data are in agreement with the functional results obtained by measuring other cholinergic parameters in the aged rat and confirm the vulnerability of cholinergic system during aging     

血清sIL—2r表达水平与脓毒血症的严重程度及预后的关系

目的：探讨脓毒血症患者血清中可溶性白细胞介素２受体（ｓＩＬ２ｒ）的表达水平以及与该病严重程度及预后的关系。方法：采用双抗体夹心酶联免疫分析法检测２９例脓毒血症患者血清ｓＩＬ２ｒ表达水平的动态变化，并以３０例正常人作为对照；用ＡＰＡＣＨＥⅡ评分方法对脓毒血症患者进行疾病严重度评分。结果：①脓毒血症患者血清ｓＩＬ２ｒ表达水平较正常人明显升高（Ｐ＜００１）；②脓毒血症患者中死亡者与存活者的血清ｓＩＬ２ｒ表达水平比较，感染初期及晚期死亡者明显高于存活者（Ｐ＜００５）；③以本组患者感染ｄ１的ＡＰＡＣＨＥⅡ评分的中位数１６为分界点，将患者分为２组，２组的血清ｓＩＬ２ｒ水平有显著差别（Ｐ＜００５）。结论：脓毒血症患者血清ｓＩＬ２ｒ表达水平明显升高；该指标与脓毒血症患者的疾病的严重程度及预后有密切的关系。此项指标的检测对判断脓毒血症患者的病情严重度及预后可能有重要意义     

Up-regulation of nicotinic acetylcholine receptors following chronic exposure of rats to mainstream cigarette smoke or α4β2 receptors to nicotine

Smokers are reported to have a higher density of central nicotinic acetylcholine receptors (nAChRs) that non-smokers at autopsy. Whether this increased receptor density is a response to smoking or a result of genetic variability is not known. While sub-chronic treatment of rats and mice with nicotine results in upregulation of central nAChRs, changes in receptor density in response to cigarette smoke have not been studied previously. In this study, male Sprague-Dawley rats were exposed nose-only for 13 weeks to mainstream cigarette smoke followed by assessment of [³H]nicotine binding in five brain regions of smoke- and sham-exposed animals. In smoke-exposed animals, there was a significant increase in nAChR density in the cortex, striatum, and cerebellum (35, 25, and 31% increases, respectively), while there was no significant change in receptor density in the thalamus and hippocampus. Smoke exposure did not alter markedly the affinity of the receptor for nicotine in these brain regions. Furthermore, up-regulation of nAChRs did not alter the biphasic binding properties by which nicotine binds to its receptor. There were no changes in the association (fast phase) or isomerization (slow phase) rate constants, and the percent contribution of slow and fast phase binding to nAChRs was not altered in the up-regulated receptor population compared with control. Similar results were observed following chronic nicotine exposure of cultured cortical cells from fetal rat brain or cells transfected with the α4β2 nAChR subtype. These results show that the up-regulation following smoke exposure in the rat is phenomenologically similar to that observed in vitro. These data provide preliminary evidence for a relationship between cigarette smoking and nAChR up-regulation in vivo and suggest that similar mechanisms of upregulation may underlie chronic smoke exposure of live animals and nicotine exposure of artificially expressed α4β2 receptors in vitro.     

Effect of pindolol on the prolactin response tod-denfluramine

We studied the effect of the 5-HT_1A receptor antagonist, pindolol, on the prolactin (PRL) response to the 5-HT releasing agent,d-fenfluramine (d-FEN), in ten healthy male volunteers. Pindolol pretreatment lowered baseline PRL levels but, when this effect was taken into account, did not significantly attenuate the PRL response tod-FEN. Within the limitations that attend the use of pindolol as a 5-HT_1A receptor antagonist, the data suggest that although 5-HT_1A receptors may play a role in the tonic release of PRL, they are not involved in the release of PRL produced byd-FEN. We propose that the PRL response tod-FEN may involve selective activation of postsynaptic 5-HT₂ receptors.     

Studies of neurotrophin biology in the developing trigeminal system

The accessibility of the primary sensory neurons of the trigeminal system at stages throughout their development in avian and mammalian embryos and the ease with which these neurons can be studied in vivo has facilitated investigation of several fundamental aspects of neurotrophin biology. Studies of the timing and sequence of action of neurotrophins and the expression of neurotrophins and their receptors in this well characterised neuronal system have led to a detailed understanding of the functions of neurotrophins in neuronal development. The concepts of neurotrophin independent survival, neurotrophin switching and neurotrophin cooperativity have largely arisen from work on the trigeminal system. Moreover, in vitro studies of trigeminal neurons provided some of the first evidence that the neurotrophin requirements of sensory neurons are related to sensory modality. The developing trigeminal system has been studied most extensively in mice and chickens, each of which has particular advantages for understanding different aspects of neurotrophin biology. In this review, I will outline these advantages and describe some of the main findings that have arisen from this work.     

Multiple sites of action of ( +)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (( +)-3PPP) in blood vessels

Functional effects of the σ ligand, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), were explored in perfused rat tail and rabbit ear arteries in vitro. In the rat tail artery (+)-3PPP inhibited contractile responses to adrenergic nerve stimulation, an effect which was reversed to potentiation by the dopamine D₂ receptor antagonist sulpiride. In the rabbit ear artery, however, (+)-3PPP potentiated contractile responses to nerve stimulation, an effect which was unchanged by sulpiride. In the rat tail artery, blockade of norepinephrine uptake by cocaine and deoxycorticosterone in the presence of sulpiride revealed two additional actions of (+)-3PPP. First, an inhibitory action on the monoamine uptake site was confirmed by direct measurement of [³H]norepmephrine accumulation. Second, at higher concentrations, an action to inhibit contractile responses to adrenergic nerve stimulation was manifested at a still unidentified site. These studies demonstrate that the observed functional effect of (+)-3PPP results from its combined actions on three individual sites with the net effect dependent on the relative densities of these different receptor sites in each type of vessel.     

Smooth muscle of rabbit isolated aorta contains the NK-2 tachykinin receptor

Summary Neurokinin A, neurokinin B and substance P caused concentration-related contractions of rabbit isolated aorta with pD₂ values of 8.1, 6.9 and 6.0, respectively. [D-Pro², D-Trp^7,9]-substance P, a competitive tachykinin antagonist, had pA₂ values of 5.3 against neurokinin A, 5.1 against neurokinin B and 5.2 against substance P indicating that tachykinin receptors mediated responses to the agonists. [pGIu⁵,MePhe⁸,-McGly⁹]-substance P 5–11 (DiMe-C7), senktide and septide did not contract the aorta. It is concluded that of the known tachykinin receptors smooth muscle of the rabbit isolated aorta contains only the NK-2 type. Send offprint requests to J. W. Constantine at the above address