兴奋大鼠延髓A1区引起降压、降心率效应的机制

在水合氯醛麻醉、箭毒化、人工呼吸的大鼠,观察到:(1) A_1区注入谷氨酸钠引起明显的血压下降和心率减慢。(2) 切断双侧颈迷走神经明显衰减A_1区的降压,降心率效应。(3) 延髓头端腹外侧区(RVL)预先注射酚妥拉明或心得安,均能明显衰减谷氨酸钠兴奋A_1区的降压效应,A_1区的降心率作用基本不受影响,将纳洛酮注入RVL后,A_1区的降压和降心率效应均无明显变化;注射荷包牡丹碱入RVL则使A_1区的降压、降心率效应反转。(4) RVL内注入酚妥拉明或心得安本身使基础血压降低,注射荷包牡丹碱入RVL则使基础血压升高(提示RVL内的α-,β-受体中介对RVE加压神经元的紧张性兴奋作用,GABA受体中介紧张性抑制作用);另一方面,RVL内注入心得安使基础心率减慢、注入纳洛酮或荷包牡丹碱使基础心率加快(说明β-受体中介紧张性心加速效应,阿片受体和GABA受体中介紧张性心抑制效应)。     

Plasma cortisol and beta-endorphin in horses subjected to electro-acupuncture for cutaneous analgesia

Electro-acupuncture (EA) treatment of horses to induce cutaneous analgesia also increased plasma concentrations of beta-endorphin (beta-EP) and cortisol. The magnitude of these increases did not relate consistently to the degree of EA-induced analgesia. Respiration and heart rates were also markedly increased during EA treatment. Intact female horses had higher packed cell volume and plasma beta-EP as well as lower plasma total protein than castrated male horses. Plasma cortisol, heart rate, and respiration rate did not differ significantly between sexes. None of the parameters measured before or during EA treatment provided an explanation for the differential cutaneous analgesia which depended on sex of subject and locus of stimulation as reported elsewhere.     

Inhibitory effect of atriopeptinergic neurons in AV3V region on angiotensinII pressor system in rat brain

In the central nervous system and the periphery, atrial natriuretic peptide (ANP) and angiotensinII(AngII) play important and opposite roles in regulating blood pressure and fluid electrolyte balance. Their central mechanisms are unclear. In the brain the anteroventral third ventricle region (AV3V) contains the most prominent collection of atriopeptin-like immunoreactive perikarya. Our previous studies show that: (1) AV3V stimulation by glutamate produces a fall in blood pressure; (2) there is an AngII pressor system composed of the lateral hypothalamus/perifornical region (LH/PF), subfornical organ (SFO), nucleus paraventricularis (NPV) and rostral ventrolateral medulla (RVL). The present study was to examine whether ANPergic projections from the AV3V could act on nuclei involved in the above-mentioned AngII pressor system. Here we demonstrate that: (1) Injection of atriopeptinIII into the LH/PF, SFO, NPV, or RVL induces a depressor response; whereas injection of normal saline has no effect. (2) Pre-injection of A 71915 (an atriopeptinIII antagonist) into the LH/PF, SFO, NPV, or RVL reverses the depressor response of the AV3V to glutamate (Glu). The results suggest that excitation of atriopeptinergic neurons in the AV3V by Glu produces an inhibitory effect on each nucleus in the LH/PF-SFO-NPV-RVL AngII pressor system.     

大鼠蓝斑内注入谷氨酸钠的心血管效应

Experiments were done on urethane anesthetized, tubocurarine immobilized and artificially ventilated rats and the following results were observed: (1) Injection of sodium L-glutamate (Glu) into locus coeruleus (LC) could evoke a pressor response, but heart rate was not significantly affected; while depressor and bradycardia effects were observed when injecting into closely adjacent areas. (2) The LC-pressor response decreased after a brain transection caudal to nucleus paraventricularis was made but remained unchanged if the transection was rostral to the nucleus; The LC-pressor response could also be attenuated by preinjection of phentolamine propranolol or atropine respectively into the rostral ventrolateral medulla (RVL). The above results suggest that LC-pressor response is not only mediated by RVL, but also by nucleus paraventricularis.     

Endorphinergic and alpha-noradrenergic systems in the paraventricular nucleus: effects on eating behavior

Brain cannulated rats were injected with the opioid peptide beta-endorphin (beta-EP) directly into the hypothalamic paraventricular nucleus (PVN) where norepinephrine (NE) is most effective in stimulating eating behavior. Beta-Endorphin (1.0 nmole) reliably increased food intake in satiated animals, and this response was blocked by local administration of the selective opiate antagonist naloxone. The eating induced by beta-EP was positively correlated in magnitude with the NE response and, like NE, was antagonized by PVN injection of the alpha-noradrenergic blocker phentolamine. Naloxone had no effect on NE-induced eating, and the dopaminergic blocker fluphenazine failed to alter either beta-EP or NE eating. When injected simultaneously, at maximally effective doses, beta-EP and NE produced an eating response which was significantly larger than either of the responses elicited separately by beta-EP or NE and was essentially equal to the sum of these two responses. The evidence obtained in this study suggests that beta-EP and NE stimulate food ingestion through their action on PVN opiate and alpha-noradrenergic receptors, respectively, and that beta-EP's action is closely related to, and in part may be dependent upon, the PVN alpha-noradrenergic system for feeding control.     

家兔伏核—杏仁核神经通路在吗啡镇痛中的作用

用辐射热照射家兔鼻嘴侧部皮肤,测量其躲避反应潜伏期作为痛反应阈,简称痛阈。通过预先埋植的慢性套管向伏核或杏仁核内进行注射,结果表明:(1)在家兔的伏核内微量注射吗啡可产生镇痛作用,该作用可被杏仁核内注射纳洛酮所削弱,并有量效依从关系;在杏仁核内注射甲啡肽抗血清(ME AS)或β-內啡肽抗血清(β-EP AS)亦可削弱上述镇痛作用;(2)在杏仁核内微量注射吗啡可产生镇痛作用,此作用不能被伏核内注射纳洛酮所阻断;(3)在伏核内注射吗啡所产生的镇痛作用可被同一部位注射γ-氨基丁酸(GAEA)受体阻断剂氯甲基荷包牡丹碱所增强,被 GABA 受体激动剂异鹅羔胺所削弱。上述结果提示:在家兔脑内从伏核到杏仁核可能存在一条与镇痛有关的神经通路,伏核内的阿片样物质及杏仁核内的甲啡肽,β-内啡肽可能参与镇痛信息的传递,而伏核内的 GABA 可能有对抗吗啡镇痛的作用。     

An inhibitory role of beta-endorphin in central cardiovascular regulation

The cardiovascular effects of beta-endorphin after administration directly into the nucleus tractus solitarii (NTS) of urethane anaesthetised rats were investigated. Unilateral injection resulted in a dose related fall in mean arterial pressure and heart rate. No change in respiratory frequency was prevented and the bradycardia reduced by pretreatment with locally applied naloxone (10 ng). This dose of the opiate antagonist had no effect on mean arterial pressure or heart rate when administered alone. Antiserum to beta-endorphin (1:50 dilution) caused a rise in pressure and a tendency towards tachycardia on injection into the NTS, while it completely blocked the depressor response and bradycardia induced by beta-endorphin. These results are consistent with the view that a beta-endorphin-like peptide has a depressor role in the central nervous system. The hypotension may result from an effect within the central connections of the baroreceptor reflex arc, probably at the level of the NTS.     

大鼠蓝斑内注入谷氨酸钠的心血管效应及其中枢机制

本工作在乌拉坦麻醉、箭毒化、人工呼吸的大鼠观察到:(1)将 L-谷氨酸钠(Glu)微量注入蓝斑(LC)引起血压升高,心率无明显变化;注入 LC 邻近区引起血压降低、心率减慢。(2)在下丘脑的室旁核尾侧断脑可衰减 LC 加压效应,而室旁核头侧断脑对 LC 加压反应无明显影响,双侧延髓头端腹外侧区(RVL)内分别注射酚妥拉明、心得安、阿托品均使兴奋 LC 引起的加压效应衰减;提示蓝斑加压效应由室旁核和 RVL(及其内的α-、β-肾上腺素能受体,M-胆碱能受体)介导。     

Inhibition of baroreflex vagal bradycardia by activation of the rostral ventrolateral medulla in rats

In stressful conditions, baroreflex vagal bradycardia (BVB) is often suppressed while blood pressure is increased. To address the role of the rostral ventrolateral medulla (RVL), a principal source of sympathetic tone, in inhibition of BVB, we microinjected DL-homocysteic acid (DLH, 6 nmol) into the RVL of chloralose-urethan-anesthetized, sinoaortic-denervated rats to examine the effect on BVB. The BVB was provoked by electrical stimulation of the aortic depressor nerve ipsilateral to the injection sites. DLH microinjection was found to suppress BVB while increasing blood pressure. The inhibition of BVB was observed even during the early phase in which DLH transiently suppressed central inspiratory activity. The inhibition was not affected either by upper spinal cord transection or suprapontine decerebration. Similar results were obtained by microinjection of bicuculline methiodide (160 pmol), a GABA antagonist, into the RVL of carotid sinus nerve-preserved rats due to withdrawal of a tonic GABA-mediated, inhibitory influence including the input from arterial baroreceptors. In conclusion, activation of the RVL inhibits BVB at brain stem level independently of central inspiratory drive.     

伏核在躯体传入冲动抑制防御性心血管反应中的作用及机制

损毁伏核可明显削弱电刺激腓深神经（ＤＰＮ）对兴奋下丘脑背内侧核诱发的升压反应和心肌缺血的抑制作用（Ｐ＜０．０５,Ｐ＜０．０１）。电刺激伏核可引起明显的降压效应。中脑中央灰质腹侧部（ｖＰＡＧ）微量注射纳洛酮可明显衰减伏核的减压效应;损毁ｖＰＡＧ甚至可翻转伏核的减压效应,引起轻度升压（Ｐ＜０．０１）。损毁弓状核后伏核的减压效应基本消失,弓状核内微量注射纳洛酮明显衰减伏的的减压效应。故ＤＰＮ传入冲动可能     

慢性应激性高压大鼠中刺激弓状核引起的压作用

Hypertension was induced by chronic foot-shock and noise stress in adult male Sprague-Dawley rats. Microinjection of 0.3 microliters (150 mmol) sodium glutamate (Glu) into the nucleus arcuatus (ARC) elicited a significant depressor effect in rats with chronic stress-induced hypertension. The depressor effect induced by excitation of ARC neurons was attenuated significantly by microinjection of 0.3 microliters beta-endorphin antiserum (beta-EPAS) into the dorso-medial periaqueductal gray (PAG) or 0.1 microliters into the area of locus coeruleus (LC) due to blockage of beta-endorphinergic fibres from ARC to PAG or LC.     

N-acetyl-beta-endorphin1-31 antagonizes the suppressive effect of beta-endorphin1-31 on murine splenocyte proliferation via a naloxone-resistant receptor.

High affinity binding sites for beta-endorphin1-31 (beta-EP) have been observed on transformed mononuclear cells such as the human U937 monocyte-like cell line and the murine EL4-thymoma line, and on normal murine splenocytes. Binding of beta-EP at these sites is resistant to competition by naloxone and other opiate receptor ligands but sensitive to N-acetyl-beta-endorphin1-31 (N-Ac), cations and GTP-gamma-sulfate. Thus, the following studies were done to determine the functional significance of binding beta-EP and N-Ac. beta-EP suppressed phytohemagglutinin (PHA)-stimulated [3H]thymidine uptake in a dose-dependent, naloxone-insensitive fashion. beta-Endorphin1-27, (des)-tyrosine beta-endorphin2-31, or N-Ac failed to duplicate the suppressive effect of beta-EP. However, N-Ac, which is equipotent to beta-EP at displacing 125I-beta-EP bound to murine splenocytes or U937 cells, antagonized the suppressive effect of beta-EP. Taken together with previous binding studies, the present observations suggest that beta-EP effects receptor-mediated responses on normal immunocytes that do not depend on the activation of neuronal-like opiate receptors which are naloxone-sensitive. N-Ac, which shows minimal binding to such brain opiate receptors, is a potent functional antagonist of the naloxone-insensitive immunocyte receptor for beta-EP.     

Effects of third ventricular injection of beta-endorphin on luteinizing hormone surges in female rat: sites and mechanisms of opioid actions in the brain

The effects of third ventricular injection of beta-endorphin (beta-EP) on spontaneous, brain stimulation-induced and estrogen-induced LH surges were studied in the adult female rat. It was found that beta-EP blocked the preovulatory surge of LH release and ovulation, while it did not affect LH release in response to LH-RH injection. The site of the beta-EP blockade of ovulation was proved to be in the brain. Beta-EP completely blocked ovulatory LH release induced by the electrochemical stimulation of the medial amygdaloid nucleus and medial septum-diagonal band of Broca, but failed to block ovulation due to the stimulation of the medial preoptic area (MPO) or median eminence, though serum LH levels after the MPO stimulation were inhibited by beta-EP. In the spayed rats treated with estradiol benzoate (EB) on Day 1 and 4 of experiment, beta-EP given on Day 5 blocked the LH surge that normally occurred on that day and led to a compensatory surge of LH on the following day. Moreover, the LH surge on Day 5 was inhibited by beta-EP given either on Day 1 or Day 4. Present data suggest that beta-EP may act in inhibiting the preovulatory LH surges not only by suppressing the preoptic-tuberal LH-RH activities but also by affecting the initiation and development of stimulatory feedback of estrogen in the central nervous system.     

大鼠延髓A5区降压、降心率效应的机制及其与A1区之比较

在与上一篇论文(关于A_1区)相同的条件下,(1) 用谷氨酸钠兴奋大鼠A_5区,和A_1区类似,也产生明显的降压、降心率效应。(2) 切断双侧颈迷走神经也明显衰减兴奋A_5区的心血管作用。(3) 将不同受体阻断剂注入延髓头端腹外侧区对兴奋A_5区引起的降压,降心率反应之影响,与A_1区比较有所不同:酚妥拉明、心得安、纳洛酮和荷包牡丹碱均能明显衰减A_5区的降压、降心率效应(心得安和荷包牡丹碱甚至反转之),表明除α-,β-,GABA受体之外,阿片受体也中介A_5区的降压降心率作用。     

Effects of ovine corticotropin-releasing factor and vasopressin on plasma beta-endorphin, cortisol and behavior after minor surgery in sheep

The evidence for an analgesic effect arising from increased peripheral concentrations of beta-endorphin (beta-EP) in various animal species is controversial, and has not been fully evaluated in the sheep. To stimulate beta-EP release, ovine corticotropin-releasing factor (oCRF) and arginine vasopressin (AVP) were injected intravenously (iv) into a group of 12 out of 24 sheep, 15 min prior to minor surgery on all sheep. This brought about significant increases (P less than 0.01) in plasma beta-endorphin (beta-EP) and cortisol concentrations, relative to the non-injected control sheep, 15-30 min after injection. Ultrafiltration indicated that less than 30% of the released beta-EP immunoreactivity was present as higher molecular weight forms (mol. wt greater than 10,000) and that the majority (about 75%) of the beta-EP was probably bound to plasma proteins. By 75 min after injection there was no significant difference in plasma beta-EP or cortisol concentrations between the two groups of sheep. Consistent with previous observations the sheep showed a characteristic aversive behavior to the human handler following surgery, lasting several days. This behavior appeared to be unaffected by a pre-operative increase in peripheral plasma beta-EP, and may indicate that this increase in beta-EP was not sufficiently analgesic to block the cognitive response to the operation, or long-lasting enough to prevent the perception of post-operative soreness.     

阿片肽类物质对大鼠黄体细胞孕酮生成的影响

本文观察了外源性阿片肽对大鼠离体黄体细胞孕酮生成的影响,结果表明:β-内啡肽以剂量-反应依赖方式促进黄体细胞孕酮生成,有效浓度范围是10~(-8)-10~(-6) mol/L;强啡肽仅在浓度为10~(-6)mol/L时才显示刺激孕酮生成的作用;而甲硫-脑啡肽无明显作用。μ-阿片受体激动剂DAGO和乙基吗啡也能明显促进孕酮的生成。纳洛酮可完全阻断β-内啡肽,DAGO和乙基吗啡的作用。由于大鼠血液中β-内啡肽含量较低,而卵巢局部具有较高浓度的β-内啡肽。因此,我们认为,β-内啡肽可能在卵巢局部参与黄体细胞孕酮生成的调节,是卵巢内促黄体因子之一,这种作用可能是由μ-型阿片受体介导的。     

褪黑素对吗啡戒断小鼠下丘脑弓状核和中脑导水管周围灰质中β-内啡肽含量的影响

本文在观察腹腔注射褪黑素（melatonin,MEL）拮抗吗啡依赖小鼠纳洛酮催促戒断反应的同时,采用放射免疫分析法、免疫组织化学法,结合计算机图像处理技术,测定其对小鼠中脑导水管周围灰质（periaqueductal grey,PAG）、下丘脑弓状核（hypothalamic arcuatenucleus,Arc）中β-内啡肽（p-endorphin,β-EP）含量的影响。结果表明,MEL（80mg／kg体重）显著抑制吗啡依赖小鼠戒断反应（P〈0．05）的同时,可显著增加其中脑PAG中β-EP含量（P〈0．05）,减弱Arc中β-EP样免疫阳性反应强度（P〈0．05）。上述结果提示,MEL可提高吗啡戒断小鼠中脑PAG中β—EP含量,降低Arc中β-EP含量。     

Effect of acute ethanol on beta-endorphin secretion from rat fetal hypothalamic neurons in primary cultures

To characterize the effect of ethanol on the hypothalamic beta-endorphin-containing neurons, rat fetal hypothalamic neurons were maintained in primary culture, and the secretion of beta-endorphin (beta-EP) was determined after ethanol challenges. Constant exposure to ethanol at doses of 6-50 mM produced a dose-dependent increase in basal secretion of beta-EP from these cultured cells. These doses of ethanol did not produce any significant effect on cell viability, DNA or protein content. The stimulated secretion of beta-EP following constant ethanol exposure is short-lasting. However, intermittent ethanol exposures maintained the ethanol stimulatory action on beta-EP secretion for a longer time. The magnitude of the beta-EP response to 50 mM ethanol is similar to that of the beta-EP response to 56 mM of potassium. Ethanol-stimulated beta-EP secretion required extracellular calcium and was blocked by a calcium channel blocker; a sodium channel blocker did not affect ethanol-stimulated secretion. These results suggest that the neuron culture system is a useful model for studying the cellular mechanisms involved in the ethanol-regulated hypothalamic opioid secretion.     

Studies on opioid receptor selectivity of beta-endorphin antagonists

Opioid receptor selectivity of several beta-endorphin (beta-EP) analogs which antagonize beta-EP-induced analgesia has been assessed using partially selective binding assays. Although the apparent affinity dissociation constant of beta-EP in these assays varies from 0.2 to 360 nm, the potency of beta-EP antagonists relative to beta-EP remains largely unchanged. It is unlikely that differences in receptor affinities can account for the antagonist properties of these analogs in vivo.     

Autonomous beta-endorphin secretion from the pituitary neurointermediate lobe: in vivo studies

The existence of independent control mechanisms of beta-endorphin (beta-EP) secretion from the anterior (AP) and intermediate (NIL) pituitary lobes is now ascertained. The aim of this study was to evaluate the effect of surgical separation from the hypothalamus of the two pituitary lobes on beta-EP secretion. Two experimental models of surgical hypothalamo-pituitary disconnection were used: 1) rats with ablation of the medial basal hypothalamus (MBH); 2) rats bearing two entire ectopic pituitaries or two anterior pituitaries (APs) only, transplanted under the kidney capsule. In rats with MBH-ablation plasma beta-EP levels were significantly higher than in sham-operated controls. Plasma beta-EP levels increased in rats transplanted with entire pituitaries 3 days after surgery and were still elevated after 1 week. In rats transplanted with APs only, no significant beta-EP changes in plasma were evident. In both experimental conditions no significant difference was present in beta-LPH plasma levels. Concentrations of beta-EP in the ectopic NILs decreased gradually after transplantation. In all these results indicate that that NIL but not the AP is capable, when is disconnected from the hypothalamus, or secreting autonomously beta-EP.