Effects of vincristine sulfate on touch dome function in the rat

The responses of touch domes in hairy skin of the rat to mechanical stimulation were examined after single doses of vincristine sulfate. Within 24 h of drug administration, the mean thresholds of domes to brief mechanical pulses had increased threefold, from 5.2 +/- 2.0 to 14.2 +/- 8.8 microns. This elevated threshold was maintained for 2 weeks but by the 3rd week the domes had recovered normal excitability. Measurements of response latency suggested that the increase in receptor thresholds occurred without impulse propagation being impaired in the axons.     

Choline uptake by glomerular synapses isolated from bovine cerebellar vermis

[3H]Choline uptake was investigated in a highly enriched preparation of glomerular particles isolated from bovine cerebellar vermis. Kinetic analysis indicates that a high-affinity choline uptake system with a relatively low maximum uptake velocity is present. At a substrate concentration of 10(-7) M, [3H]choline uptake was shown to be sodium-dependent, hemicholinium-sensitive and non-reactive to increasing concentrations of unlabeled choline. These findings support the presence of a high-affinity choline uptake system in cerebellar glomeruli and would seem to be consistent with the suggestion that a small proportion of mossy fibers are cholinergic in this brain region.     

Distribution of central cholinergic neurons in the baboon (Papio papio). II. A topographic atlas correlated with catecholamine neurons

The topographic distribution of central cholinergic and catecholaminergic neurons has been investigated in the baboon (Papio papio). The perikarya were mapped on an atlas through the brain and spinal cord employing sections processed for acetylcholinesterase (AChE) pharmacohistochemistry coupled with choline acetyltransferase (ChAT) immunohistochemistry or aqueous catecholamine-fluorescence histochemistry. Compared with subprimates, there is a remarkable increase in the volume occupied by and the number of cholinergic cells contained in the nucleus basalis and nucleus tegmenti pedunculopontinus (subnucleus compacta). The elaboration of these parts of the cholinergic system is accompanied by a large extension of catecholaminergic cell groups in the midbrain (groups A8-A10), particularly the substantia nigra (pars compacta), and in the dorsolateral pontine tegmentum (A5-A7 complex). Although cholinergic and catecholaminergic soma generally occupy distinctly different regions of the brain, a close apposition of cholinergic and noradrenergic neurons occurs in the dorsolateral pontine tegmentum. In the peripeduncular region ChAT-positive cells and green fluorescent neurons of the A6-A7 complex form parallel lines and do not intermingle as has previously been demonstrated in the cat. Two distribution patterns, aggregated or disseminated, are another common feature of central cholinergic and catecholaminergic perikarya. The cholinergic neurons in the nucleus tegmenti pedunculopontinus and the catecholaminergic neurons in A6-A7 complex display both patterns. This comparative study of three transmitter systems in the baboon suggests that the cholinergic as well as the catecholaminergic neurons that give rise to ascending telencephalic and dorsal diencephalic projections undergo phylogenetic development in terms of cell number and nuclear volume.     

乙酰胆碱对脑内5-羟色胺代谢的影响

本文观察了乙酰胆碱(ACh)对大鼠脑内5-羟色胺(5-HT)代谢的影响。发现:胆碱酯酶抑制剂毒扁豆碱和ACh合成阻断剂密胆碱(HC_(-3))不仅可分别升高或降低脑内ACh的水平,而且可分别升高或降低脑内5-HT及其代谢产物5-羟吲哚乙酸(5-HIAA)的水平。认为ACh对脑内5-HT的代谢发生明显的影响。     

Immunohistochemical staining of the human forebrain with monoclonal antibody to human choline acetyltransferase

Monoclonal antibody to human choline acetyltransferase (ChAT) was successfully produced from a mouse hybridoma cell line. The antibody was found to be of the IgM molecular species. By using this monoclonal antibody, immunohistochemical staining for ChAT was obtained on human brain sections. Only large sized cells were stained in the putamen and the substantia innominata. The specificity of the staining was comparable to that with polyclonal rabbit antibody to human ChAT produced by standard immunization procedures. No staining was observed when mouse monoclonal antibodies prepared against other human or bacterial antigens, or when normal mouse IgM, was employed.     

Synthesis of lecithin (phosphatidylcholine) from phosphatidylethanolamine in bovine brain

Choline molecules are needed for the synthesis of acetylcholine and phospholipids in the mammalian brain. An enzymatic activity capable of forming lecithin (phosphatidylcholine) from the step-by-step methylation of phosphatidylethanolamine is identified in the bovine brain. This enzyme(s), phosphatidylethanolamine-N-methyltransferase (EC 2.1.1.17), is localized in the synaptosomal fraction of bovine caudate nucleus, uses S-adenosylmethionine as the methyl donor (apparent K_m = 20 μM), and has a V_max of 50–60 pmol/mg protein × h (i.e. about 1% of that found in rat liver). The brain may be able to meet some of its choline requirements by de novo synthesis.     

Choline administration to the rat increases urinary catecholamines

Summary Previous studies have shown that choline administration accelerates the synthesis of acetylcholine (ACh) in rats and raises ACh levels in brain, adrenal medulla, and other tissues receiving a cholinergic innervation. After 24 hours, this precursor-induced elevation in ACh levels causes tyrosine hydroxylase activity to increase, unless the adrenals have been previously denervated. We now report that oral choline administration also increases urinary epinephrine levels, probably by enhancing the release of the catecholamine from the adrenal gland. For four consecutive 4-day periods, male Sprague-Dawley rats received (1) no treatment, (2) water, (3) choline (20 mmoles/kg), and (4) water, and excreted 157, 200, 646, and 267 ng of epinephrine per 24-hour period, respectively. Urinary norepinephrine levels also increased on days that the animals received choline. Choline failed to increase urinary epinephrine levels among rats previously subjected to bilateral adrenal denervation; in contrast, nicotine, a direct-acting cholinergic agonist, continued to elicit this increase. Thus, choline administration apparently potentiates the increase in urinary epinephrine produced by treatments that accelerate the flow of impulses along the splanchnic nerves. These data provide additional support for the hypothesis that choline administration, by increasing presynaptic ACh levels, enhances cholinergic transmission at preganglionic synapses of the sympathetic nervous system.     

Effects of choline and glucose on atropine-induced alterations of acetylcholine synthesis and content in the caudate nuclei of rats

Atropine-induced decrease in the concentration of acetylcholine (ACh) in the brain can be diminished by pretreating the animals with a large dose of choline^72,73. The injected choline might act by improving the supply of substrate for the synthesis of ACh, or by competing with atropine for presynaptic muscarinic receptors and thus decreasing the release of ACh. Since, under in vitro conditions, changes in the release of ACh are reflected by changes in its synthesis, experiments have been performed on slices of rat caudate nuclei to check whether an increase in the extracellular concentration of choline causes a decrease in the atropine-induced stimulation of ACh synthesis. The rate of [¹⁴C]ACh synthesis from [¹⁴C]glucose was faster in the presence of 530 μM than 30 μM choline, and 5 μM atropine stimulated the synthesis of [¹⁴C]ACh more at 530 μM than at 30 μM choline in the medium. These observations substantiate the view that the administration of choline in vivo acts by supporting the synthesis of ACh, rather than by inhibiting its release.

In subsequent experiments on rats in vivo, an attempt has been made to influence the ACh-depleting action of atropine by pretreatment with a large dose of glucose as a distant precursor of acetyl-CoA, the second substrate for the synthesis of ACh. The administration of atropine (25 mg/kg) diminished the content of ACh in the caudate nuclei by 48%; if the injection of atropine followed after an injection of glucose (20.2 mmol/kg), the content of ACh was diminished by only 25%. It appears likely that glucose acted by improving the availability of acetyl-CoA for the synthesis of ACh and that the supply of either precursor of ACh (i.e. choline and acetyl-CoA) may become rate-limiting when the demands on the synthesis of ACh in the brain are increased.     

Monoaminergic, peptidergic, and cholinergic afferents to the cat facial nucleus as evidenced by a double immunostaining method with unconjugated cholera toxin as a retrograde tracer

Using a sensitive double immunostaining technique with unconjugated cholera-toxin B subunit as a retrograde tracer, the authors determined the nuclei of origin of monoaminergic, peptidergic, and cholinergic afferent projections to the cat facial nucleus (FN). The FN as a whole receives substantial afferent projections, with relative subnuclear differences, from the following areas: 1) the perioculomotor areas, the contralateral paralemniscal region, and the mesencephalic reticular formation dorsal to the red nucleus; 2) the ipsilateral parabrachial region and the nucleus reticularis pontis, pars ventralis; and 3) the nuclei reticularis parvicellularis, magnocellularis, ventralis, and dorsalis of the medulla. In addition, the present study demonstrated that the lateral portion of the FN receives specific projections from the contralateral medial and olivary pretectal nuclei and the ipsilateral reticular formation of the pons. It was also found that the FN receives: 1) serotoninergic inputs mainly from the nuclei raphe obscurus, pallidus, magnus, and the caudal ventrolateral bulbar reticular formation; 2) catecholaminergic afferent projections from the A7 noradrenaline cell group located in the K?lliker-Fuse, parabrachialis lateralis, and locus subcoeruleus nuclei; 3) methionin-enkephalin-like inputs originating in the pretectal complex, the nucleus paragigantocellularis lateralis and the caudal raphe nuclei; 4) substance P-like afferent projections mainly from the Edinger-Westphal complex and the caudal raphe nuclei; and 5) cholinergic afferents from an area located ventral to the nucleus of the solitary tract at the level of the obex. In the light of these anatomical data, the present report discusses the physiological significance of FN inputs relevant to tonic and phasic events occurring at the level of the facial musculature during the period of paradoxical sleep in the cat.     

瑞芬太尼和丙泊酚对老年大鼠学习记忆的影响

目的:探讨瑞芬太尼和丙泊酚对老年大鼠学习记忆及其海马胆碱乙酰转移酶(ChAT)表达的影响。方法:雄性18月龄SD大鼠50只,随机分成5组(n=10):对照1周组(N1组),瑞芬太尼1周组(R1组),丙泊酚1周组(P1组),对照3周组(N3组),丙泊酚3周组(P3组)。R1组尾静脉注射瑞芬太尼60μg/kg,随后静脉泵注15μg/(kg.min),维持1h。P1、P3组腹腔注射60 mg/kg丙泊酚,待出现翻正反射时追加1/2首剂量,共追加2次。N1、N3组腹腔注射等量生理盐水。N1、P1、R1组于处理后第1周行Morris水迷宫实验,N3、P3组处理后第3周行水迷宫实验,每天4次,连续4 d。测试结束后灌注固定取脑,行海马组织切片的HE染色和免疫组化染色,观察海马结构及测定海马ChAT的表达。结果:①水迷宫结果:潜伏期测试各组同一时间点与对照组比较,仅在第1周的第2 d和第3 d,P1组较N1组差异有统计学意义(P<0.01或P<0.05);探索试验中通过原平台次数各组与对照组比较在第1周和第3周均无统计学意义(P>0.05)。②海马HE染色:光镜下各组大鼠海马结构未见明显异常。③海马免疫组化染色:海马CA1区ChAT阳性表达细胞数各组与对照组比较均无统计学意义。结论:麻醉剂量的丙泊酚可致老年大鼠短期学习记忆障碍,瑞芬太尼无此作用。丙泊酚和瑞芬太尼麻醉后4 d或3周对大鼠海马ChAT的表达无影响。