PEPTIDES AS NEUROTRANSMITTERS IN VASCULAR AUTONOMIC NEURONS

1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co-localized with non-peptide transmitters and sometimes with other peptides. 2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation (>2–5 Hz) with trains of impulses. 3. Neuropeptides can have potent post-synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature. 4. Post-synaptic effects of neuropeptides tend to be more slowly-developing and more long-lasting than those of non-peptide transmitters. 5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non-peptide transmitters and the slower phases mediated predominantly by one or more neuropeptides. 6. Some neuropeptides do not seem to have post-synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release. 7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.     

Control of feeding and sexual behaviors by neuropeptide Y: physiological implications

Recent evidence suggests that a variety of hypothalamic neuropeptides may mediate interneuronal communication to coordinate diverse neuroendocrine and behavioral functions. In this work, we describe the effects of neuropeptide Y (NPY) on feeding and sexual behaviors. We observed that central administration of bolus NPY stimulated a robust, dose-related feeding response in satiated male and female rats. Continuous NPY receptor activation also evoked dose-related, intermittent feeding in a manner normally observed during nocturnal feeding. It appears that the paraventricular nucleus in the hypothalamus may be the primary site of NPY action because the anticipated reciprocal changes in NPY concentrations, in response to food deprivation followed by ad libitum food intake, occurred only in this site. Additional findings revealed that NPY-induced feeding may follow either substantial reduction or complete restraint of an inhibitory influence on feeding mediated by alpha 2-adrenoreceptor systems in satiated rats. Further, NPY was found to suppress male and female sexual behaviors. The suppressive effects on sexual behavior were apparent prior to or at the time of the onset of feeding after NPY administration. These observations may provide a neurochemical basis for clinical and animal studies on disorders of feeding associated with diminished reproductive functions.     

老龄大鼠膀胱逼尿肌对神经递质反应的研究

目的 探讨老年排尿功能障碍的神经机制。方法 利用水浴条件下离体逼尿肌条张力测定技术，观察老龄Wistar大鼠膀胱逼尿肌条对不同浓度卡巴可、去甲肾上腺素、ATP的收缩反应改变；阿托品对卡巴可诱导逼尿肌收缩的舒张反应改变；异丙肾上腺素对电刺激诱导逼尿肌收缩的舒张反应改变。结果 与青龄组相比，老龄大鼠膀胱逼尿肌对ATP的收缩反应显著增强，对异丙肾上腺素的舒张反应在高浓度时增强；对卡巴可、阿托品、去甲肾上腺素的反应没有差异。结论 老龄大鼠排尿功能障碍可能与β-肾上腺素能、嘌呤能神经改变有关。     

补益中药对老龄雄性大鼠下丘脑神经递质——甲状腺轴机能作用的研究

本文通过对3月龄、18月龄、24月龄雄性大鼠下丘脑去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA),和下丘脑垂体促甲状腺释放激素(TRH)、垂体、血甲状腺释放激素(TSH)、血甲状腺激素(T_3、T_4)的测定,研究了大鼠下丘脑神经递质与甲状腺轴机能的增龄性变化,并在此基础上探讨了补益中药对老龄大鼠下丘脑—垂体—甲状腺机能的作用。结果提示:老龄大鼠下丘脑机能的减退是甲状腺轴机能减退的重要原因;补益中药可能改善了老龄大鼠下丘脑的调控机能,进而延缓了甲状腺轴机能的老年性变化。     

Enrichment of Glutamate-like Immunoreactivity in Primary Afferent Terminals Throughout the Spinal Cord Dorsal Horn

Although several lines of evidence indicate that glutamate is a neurotransmitter in primary afferent terminals, controversies exist on the proportion and types of such terminals that release glutamate. In the present study quantitative analysis of immunogold labelling was used to assess the presence of glutamate-like immunoreactivity in primary afferent terminals in laminae I – V of the rat spinal cord dorsal horn. Anterograde transport of choleragenoid – horseradish peroxidase from a spinal ganglion and tetramethyl benzidine histochemistry were used to identify primary afferent terminals in laminae I and III – V. Presumed C-fibre terminals in lamina II were identified on morphological criteria (dense sinusoid axon terminals). Primary afferent terminals in all dorsal horn laminae displayed significantly higher levels of glutamate-like immunoreactivity than pleomorphic vesicle-containing profiles in laminae III – IV and large neuronal cell bodies in laminae III – V. The density of gold particles over primary afferent terminals also significantly exceeded the average density of gold particles over laminae II and III – IV. The highest densities of gold particles were present over dense sinusoid axon terminals in lamina II. These findings suggest that glutamate, alone or in combination with other neuroactive compounds, is involved in the transfer of all sensory modalities from primary afferent fibres to dorsal horn neurons.     

糖尿病大鼠视网膜基因表达谱差异的初步分析

目的 建立大鼠正常视网膜和糖尿病8周视网膜基因表达谱，比较两者差异，初步分析糖尿病视网膜病变的相关基因。方法 通过限制片段差异显示 PCR（ restriction fragments differential display-PCR，RFDD-PCR）获得正常大鼠视网膜及8周糖尿病大鼠视网膜组织转录组片段。应用Fraent Analysis等软件，对差异片段进行生物信息学分析，初步确定糖尿病视网膜病变相关基因／表达序列标签（ expression sequence tag, Ksr）。结果 获得有意义的片段共3639个，有差异的片段840个，占表达数的23．08％。其中包括5个视觉传导相关基因，13个兴奋性神经递质受体基因和3个抑制性神经递质受体基因。糖尿病8周大鼠视网膜Rhodopsin kinase,β-arrestin,Phosducin, rod photoreceptor cGMP-gated channel 和 Rpe65的表达下调，离子型谷氨酸受体iGluR1-4下调，代谢性谷氨酸受体及γ-氨基丁酸受体各亚型则普遍上调，而甘氨酸受体表达无变化。结论 糖尿病8周大鼠神经视网膜已受到累及，其基因表达模式的改变，可能与糖尿病早期视功能损害有关。     

Effect of cyclic GABA derivative TZ-146 on the content of neurotransmitters in rat brain stem

The effect of cyclic GABA derivative TZ-146 on the content of catecholamines, serotonin, their metabolites, and neurotransmitter amino acids in rat hypothalamus and brain stem was studied by high-performance liquid chromatography with electrochemical detection. Opposite changes in the content of homovanillic acid, aspartate, glutamate, and glycine in the examined structures were accompanied by inhibition of dopamine metabolism. Possible participation of cerebral glutamatergic system in the effect of TZ-146 is discussed. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 5, pp. 544–546, May, 2000     

李仲愚杵针刺激大鼠"足三里”穴区对中枢单胺类神经递质含量的影响

为探讨李仲愚杵针针刺镇痛效应的中枢作用机制,了橇针对正常大鼠及腹腔注射对氯苯丙氨酸大鼠的不同脑区单胺类递质水平的影响,并与是针作比较。结果显示：杵与电针一样,在刺激大鼠“足三里”穴区后,能明显提高间脑和端脑５－羟色胺与５－羟醋酸吲哚的含量,同时也可使间脑去甲肾上腺素含量明显下降,杵针对端脑的ＮＥ以及两脑区多巴胺的影响未见明显的影响。腹腔注射ＰＣＰＡ后大,大鼠脑内Ｔ－ＨＴ、５－ＨＩＡＡ含量均明显下降     

Lamotrigine-antiparkinsonian activity by blockade of glutamate release?

Summary Recent experiments provide evidence that the NMDA-antagonist MK-801 has a locomotor-stimulating effect in monoamine-depleted rodents. These findings are based upon a hypothetical pathway-circuit including the basal ganglia as a model reflecting hypo- and hyperkinetic movement disorders. We have treated 5 patients suffering from Parkinson's disease with the antiepileptic drug lamotrigine which does not appear to be an NMDA-antagonist but acts functionally as a glutamate antagonist by inhibition of presynaptic glutamate release.     

Tunicamycin Dissociates Depolarization-induced Calcium Entry From Transmitter Release. Involvement of Glycosylated Protein(s) in the Process of Neurosecretion in PC-12 Cells

The process of regulated secretion in PC-12 cells is tightly coupled to calcium entry, which is absolutely dependent on extracellular Ca2+([Ca2+]ex). Tunicamycin treatment of the cells dissociated depolarization-triggered Ca2+ influx from depolarization (high K+)-induced transmitter release into two distinct and independent phases. Deplarization-evoked Ca2+ influx was not affected by tunicamycin treatment (1 microg/ml, 72 h), whereas depolarization-evoked transmitter release was strongly inhibited (> 60%), suggesting at least a two-step process, and the participation of glycosylated protein(s) in the actual fusion/secretion step. Similarly, bradykinin-mediated transmitter release was linearly related to and absolutely dependent on Ca2+ entry, and was inhibited by tunicamycin treatment (> 80%), whereas bradykinin-evoked Ca2+ entry was not impaired, indicating that glycosylated protein(s) are essential for bradykinin-evoked release at a step subsequent to Ca2+ influx. The heavily glycosylated alpha2 subunit of the dihydropyridine-sensitive channel, which was used to monitor tunicamycin inhibition of glycosylation, was not expressed in the tunicamycin-treated cells, as shown by Western blot analysis. This observation allowed us to conclude that the alpha1 subunit of the heteromeric dihydropyridine voltage-sensitive Ca2+ channel, which is responsible for Ca2+ entry, is also fully functional when not assembled with its corresponding alpha2 subunit. The molecular properties of the alpha2 subunit, whose role in the complex structure of the channel is not yet understood, are shown for the first time for the L-type Ca2+ channel of PC-12 cells. Similar to cardiac and skeletal muscle cells, the alpha2 subunit appears to be a glycosylated polypeptide of molecular weight 170 kD and to display a characteristic mobility shift to 140 kD under reducing conditions.