Endothelin in coronary artery disease

Abstract

Objectives. The aim of the present study was to compare changes in circulating levels of proopiomelanocortin (POMC) derivates and lactate after remote ischemic preconditioning (IPC) and physical exercise. Introduction. Remote IPC (rIPC) is cardioprotective following acute myocardial infarction and major cardiac surgery. A blood-borne, transferable factor, released following not only rIPC but also vigorous exercise, mediates protection that is abolished by naloxone suggesting involvement of an opioid-receptor-dependent pathway. Design. Eight healthy volunteers underwent rIPC by four cycles of 5-min inflation of a pneumatic tourniquet to 200 mmHg interrupted by 5 min of deflation. Subsequently, circulating plasma levels of POMC derivates, cortisol, and lactate were measured. After 3 days, the volunteers completed a vigorous exercise program, after which the same compounds were measured. Results. While rIPC was not associated with any significant increase in circulating POMC derivates or lactate, exercise induced significant elevation of both compared with baseline. Conclusions. We were not able to demonstrate a detectable increase in circulating POMC derivates by a standard rIPC stimulus, suggesting that rIPC effect is not mediated by local or detectable central release of these derivates.     

磁场对血浆β－内啡肽的影响

目的探讨旋转的恒定磁场（即交变磁场）对神经内分泌活动的影响及与止痛的关系，从而探索磁场止痛的机理。方法实验采用本实验室研制的ＷＤ６０００多功能治疗仪，其恒定磁场强度为０．６Ｔ，转速为２４０转／分，对新西兰兔及疼痛病人进行磁场处理，并分别在磁场处理前后抽取血样，同时用放射免疫方法测定其血浆中β－内啡肽含量。结果磁场能促使其血浆β－内啡肽显著升高。结论此种变化是构成磁场止痛的内在基础之一。     

Opioid peptides as regulators of acetylcholinesterase activity

I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR I.P. Ashmarin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 10, pp. 457–459, October, 1989.     

Contribution of brainstem GABAergic circuitry to descending antinociceptive controls: II. Electron microscopic immunocytochemical evidence of GABAergic control over the projection from the periaqueductal gray to the nucleus raphe magnus in the rat

Pharmacological, physiological, and behavioral studies suggest that inhibitory GABAergic neurons influence the projection from the midbrain periaqueductal gray matter to the medullary nucleus raphe magnus. The present study used electron microscopic immunocytochemical techniques to examine the morphology and synaptic relationships of GABA-immunoreactive terminals in the ventrolateral periaqueductal gray. These putative GABAergic terminals comprise almost 40% of all axon terminals in the periaqueductal gray. GABA-immunoreactive terminals contain small, clear, pleomorphic or round, vesicles, and 46% also contain some dense-cored vesicles. In some experiments we also used a colloidal gold-conjugated retrograde tracer to label periaqueductal gray neurons that project to the nucleus raphe magnus. About half of the synaptic inputs onto the cell bodies and proximal dendrites of retrogradely labeled neurons are GABA-immunoreactive; these putative GABAergic synapses, which directly control activity in neurons projecting from the periaqueductal gray to the nucleus raphe magnus, might mediate the antinociception-related effects of exogenous GABAA receptor ligands.     

ACE在皮肤组织损伤修复与再生中作用的研究

血管紧张素转化酶（angiot ensin-converting enzyme,ACE）是肾素-血管紧张素系统（renin-angiotensin system,RAS）激活过程中的关键性限速酶之一,可催化血管紧张素Ⅰ水解生成RAS最重要的活性产物血管紧张素Ⅱ。ACE也可使具有扩张血管反应的缓激肽生成苯丙-精二肽,还可直接作用于肾上腺皮质促进醛固酮分泌。近年来发现ACE除了降解血管紧张素I和缓激肽外,还能降解其它产物如：β-内啡肽、P物质、Ac-SDPK等。同时,ACE和中性内肽酶（neutral endopeptidase,NEP）作为终止皮肤神经-内分泌介质作用的关键酶可调控皮肤细胞的存活、创伤愈合和组织再生。本文主要阐述近年来有关ACE及其底物在皮肤组织损伤修复与再生中作用的相关研究。     

A selective effect of naloxone on heterosynaptic C-fibre-mediated inhibitions in the rat dorsal horn

The effect of naloxone on C-primary afferent-mediated inhibitions of C-fibre-evoked activity in deep dorsal horn neurones has been examined in decerebrate-spinal rats. The same C-afferents that evoke activity in a given neurone can inhibit that C-evoked activity (homosynaptic inhibition), and C-afferent input can also inhibit the activity evoked in dorsal horn neurones by other C-afferents (heterosynaptic inhibition). Naloxone was found to selectively reverse heterosynaptic C-mediated inhibitions without affecting homosynaptic inhibitions. In several neurones the heterosynaptic inhibitions were completely abolished by naloxone. These results show that homo- and heterosynaptic C-mediated inhibitions operate by different mechanisms and that, at least in some neurones, endogenous opioids are likely to be the major inhibitory transmitters involved in producing the heterosynaptic inhibition of the activity evoked by one C-input by another C-input.     

新生儿缺氧缺血性脑病脑脊液β-内啡肽和强啡肽1-13

通过放射免疫分析法测定新生儿缺氧缺血性脑病脑脊液中β－内啡肽（β－ＥＰ）和强啡肽１－１３（ＤｙｎＡ１－１３）的含量变化，结果表明，β－ＥＰ在患儿组含量显著升高，ＤｙｎＡ１－１３则明显降低，并与脑损伤程度有关．还发现，β－ＥＰ含量在发病７２ｈ内升高最著，４～７ｄ下降，１０～１５ｄ基本恢复正常，ＤｙｎＡ１－１３含量变化，则呈相反趋势，提示，两种阿片肽可能参与新生儿缺氧缺血性脑病病理生理过程．并为临床判断新生儿缺氧缺血性脑病病情、预后、疗程提供了参考依据．     

强啡肽A（1－17）致大鼠脊髓损伤

为研究脊髓损伤及继发性损伤的发病机理及其治疗方法，建立了蛛网膜下腔注射强啡肽Ａ（ＤｙｎＡ）致大鼠脊髓损伤动物模型。发现内源性ＤｙｎＡ（１－１７）的氨基端酪氨酸与竣基端的氨基酸残基在致脊髓损伤中都是重要的：Ｎ－甲基－Ｄ－天冬氨酸受体拮抗剂ＤＬ－２－氨基－５－胯酰戊酸（ＡＰＶ），犬尿氨酸及ＭＫ－８０１在对抗ＤｙｎＡ的损伤中均有一定的疗效。但ＡＰＶ和ＭＫ－８０１本身有一定毒性。而犬尿酸氨是一种内源性物质，主要作用于甘氨酸Ｂ变构调节位点，对整体生理功能影响较小。钙拮抗剂维拉帕米对抗强啡肽的致脊髓损伤作用迅速而完全。在所用剂量（５０ｎｍｏｌ）下无毒副作用。     

Interleukin-1 interaction with neuroregulatory systems: selective enhancement by recombinant human and mouse interleukin-1 of in vitro opioid peptide receptor binding in rat brain

Interleukin-1 (IL-1) exerts a wide variety of biological effects on various cell types and may be regarded as a pleiotropic peptide hormone. Biological evidence suggests that IL-1 participates in the modulation of central nervous system physiology and behaviour in a fashion characteristic of neuroendocrine hormones. In this investigation, recombinant (r) human (h) IL-1 and r mouse (m) IL-1 were examined for their modulation of opioid peptide receptor binding in vitro. Experiments were performed on frozen sections of rat brain. Receptor binding of radiolabeled substance P and of radiolabeled neurotensin were not significantly affected by the presence of rIL-1s. Recombinant IL-1s, however, significantly enhanced specific binding of 125I-beta-endorphin (125I-beta-END) and of D-ala2-(tyrosyl-3,5-3H)enkephalin-(5-D-leucine) (3H-D-ALA), equipotently and in a concentration-dependent manner with maximal activity occurring at a concentration of 10 LAF units/ml. The increased binding of 125I-beta-END and 3H-D-ALA was blocked steroselectively by (-)-naloxone and by etorphine, suggesting detection of opiate receptors. In addition, brain distribution patterns of receptors labeled in the presence of rIL-1s corresponded to patterns previously published for opiate receptors. Autoradiographic visualization of receptors revealed that rIL-1s in the different areas of the brain exert their effect on opioid binding with comparable potencies. The data suggest that certain central nervous system effects of IL-1s may be mediated by their selective interaction with opiatergic systems at the receptor level.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relevance to clinical care of recent research in neurobiology

Progress continues to be made in clarifying neurobiological factors in alcoholism and other chemical dependencies. Research in animal behavioral genetics and human genetics has revealed substantial genetic predispositions for some cases of alcoholism. Studies of neurotransmitters suggest that some alcoholics may have antecedent deficiencies in one or more important neurochemical systems. Cocaine dependence is considered to be related to biphasic change in sopaminergic neurons and receptor systems. Condensation products such as salsolinol, tetrahydropapaveroline, and beta carbolines can alter alcoholic preference and motivate heavy ethanol consumption in animals. However, hypothesized theoretical mechanisms underlying such increased drinking with infusions of condensation products are unclear and may require revision. New pharmacological treatments stemming from advances in neurobiological research have been applied successfully to treatment of withdrawal states, but none have been demonstrated to be appropriate for long-term maintenance of abstinence.