摘要:

AbstractAcid hydrolysis of mouse caudate homogenates results in a significantly increased concentration ofpara‐hydroxyphenylacetic acid (p‐HPAA). Thusp‐HPAA appears to be significantly present as an acid‐labile conjugate in the mouse caudate nucleus. Saline injection also increased the concentration of the acid metabolite of the tyramines.The subcutaneous injection of eithermeta‐hydroxyphenylacetic acid (m‐HPAA) orp‐HPAA or both produced at 0.5 hr and 2.0 hr large increases in the mouse caudate nucleus concentrations ofm‐ and/orp‐HPAA. Similarly at 2.0 hr the injection of a combination ofpara‐ andmeta‐tyramine caused large increases in the acid metabolite concentrations.Probenecid, at a dose of 500 mg/kg, increased striatalp‐HPAA andm‐HPAA concentrations. Probenecid, injected prior to the administration ofp‐HPAA andm‐HPAA, did not reduce the increased concentrations of these two acid metabolites previously observed after the administration of the acid metabolites alone. It thus appears thatp‐HPAA andm‐HPAA are transported from the brain by a probenecid‐sensitive mechanism, but in the presence of high blood concentrations,p‐HPAA andm‐HPAA may enter the brain by a mecha

ISSN:0360-4012    

DOI:10.1002/jnr.490100202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractIn order to investigate the in vivo pharmacological effects of the drug naftidrofuryl, we prepared populations of synaptic and nonsynaptic mitochondria from rat brain cortex. In these different mitochondrial populations the activities of citrate synthase, malate dehydrogenase, total NADH cytochromecreductase, cytochrome oxidase, and glutamate dehydrogenase were evaluated. Except for glutamate dehydrogenase, the specific activities of the enzymes evaluated in the „free”︁ mitochondrial fraction were higher than those observed in the „synaptic”︁ SM1 and SM2 mitochondrial fractions, the difference between SM1 and SM2 fractions being significant. The in vivo administration of naftidrofuryl induced few and different changes in the various mitochondrial

ISSN:0360-4012    

DOI:10.1002/jnr.490100203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractIn order to better characterize the presynaptic GABA receptors regulating glutamate release in the cerebellum [Levi and Gallo, 1981], a number of GABA agonists and GABA transport inhibitors were tested for their ability to potentiate the depolarization‐induced release of the glutamate analog D‐[3H]aspartate from superfused cerebellar synaptosomes. Of all the compounds tested, only those which are known to interact specifically with GABA receptors were effective when tested on synaptosomal preparations. The order of effectiveness found was the following: muscimol ≃ 3‐APS≥P4S>isoguvacine>THIP. GABA uptake inhibitors were unable to enhance D‐[3H]aspartate evoked release from synaptosomes, but were effective when tested in cerebellar slices; in the latter case, the activation of the GABA receptors may be achieved indirectly, through an increase of the extracellular GABA concentrations. The substrate specificity of the presynaptic GABA receptors regulating cerebellar acidic amino acid release appears to be similar to that reported for GABA receptors in radioligand binding studies and for GABA autoreceptors. Studies on synaptosomes from immature cerebella suggested that the presence of the potentiating effect on the acidic amino acid release by GABA agonists is correlated with the development of the parallel fiber terminals, which are believed to be the main site from which glutamate is released in the adult

ISSN:0360-4012    

DOI:10.1002/jnr.490100204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThe natural substrate for sphingomyelinase contains hydrophobic and polar moieties. In this study, we have employed pH rate studies and examined hydrophobic compounds and phosphorylated esters for their effect on sphingomyelinase activity in an attempt to determine some of the kinetic properties of this enzyme. Sphingomyelinase, purified from human placentae, undergoes noncompetitive inhibition by octylglucoside and Nonidet P‐40, two nonionic detergents containing terminal octyl groups. The effect of these detergents at the hydrophobic binding site is somewhat different from that of Triton X‐100, which contains an isooctyl terminal group, and this may serve to identify a structural basis for the effects.Sphingomyelinase activity is also modulated by several nucleotides. Inhibition by 5′‐adenosine monophosphate (5′‐AMP) is also noncompetitive. Other nucleotide monophosphates (such as 5′‐uridine monophosphate (5′‐UMP), 5′‐cytidine monophosphate (5′‐CMP), 2′‐adenosine monophosphate (2′‐AMP), and 3′‐adenosine monophosphate (3′‐AMP) and phosphorylated intermediates (such as phosphorylcholine, phosphorylethanolamine and hexose phosphates) have a lower inhibitory effect. The data suggest that the inhibition by 5′‐AMP involves the combined effect of the phosphate group and the purine ring, structural requirements which may also be satisfied by bis(4‐methylumbelliferyl)phosphate, a synthetic enzyme substrate.Studies of pH rate indicate that the maximal velocity for the hydrolysis of sphingomyelin is independent of pH over the range 3.5–6.2 while the Kmvalue shows a pH dependence. The Kmvalue is lowest from pH 4.0–5.2 and rises at pH values outside this range. The log Vmax/Kmand pKmrelationships, when plotted as a function of pH, have been used to identify the dissociation constants for the binding of sphingomyelin by the enzyme. These occur at pK values of 4.1 and 5.5. The activity of sphingomyelinase is also reduced when the enzyme is photooxidized in the presence of methylene blue or rose bengal and carbamylated by diethylpyrocarbonate (DEPC).These results are interpreted to show that (1). the ezyme contains a hydrophobic binding site which involves linear aliphatic moieties containing at least eight carbon atoms; (2) two ionic groups are involved in formation of the enzyme substrate complex, one of which is presumed to be the carboxylate group of aspartate or glutamate (represented by pK 4.1) and the second may be the protonated imidazolium group of histidine (represeted by pK 5.5); and 3) since the maximal velocity shows no pH dependence, the interactions involving the hydrophobic and ionic groups affect only the binding of te substrate to the

ISSN:0360-4012    

DOI:10.1002/jnr.490100205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThe distribution and heterogeneity of cholecystokinin (CCK) in different regions of the central nervous system (CNS) of 12 adult rats and six cows was determined by means of specific radioimmunoassays. In addition, the biologic activity of immunoreactive material was evaluated in a bioassay that used a rabbit gallbladder‐strip preparation. High amounts of immunochemically detectable CCK‐8 (20.2 ± 1.5 pmol/g) and CCK‐33 (33.7 ± 3.3 pmol/g) and of biologically active CCK were found in the telencephalon, although concentrations decreased progressively from the rostral to the caudal portions of the brain. The distribution and biologic activity of CCK was similar in rat and cow brain. Ratios of biologic to immunologic activity ranged from 1.0 to 8.0 and were higher for CCK‐8 than for CCK‐33. The results indicate that (1) CCK‐8 and CCK‐33 immunoreactivity are widely distributed throughout the CNS in a unique and differential manner; (2) CCK is biologically active in all the regions of the brain, with a pattern of distribution similar to that found with radioimmunoassay; (3) measurable bioactivity was equal to or greater than measurable immunoreactivity in all areas of the brain in rat and cow; and (4) CCK is present in tissues without significant species differences betw

ISSN:0360-4012    

DOI:10.1002/jnr.490100206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractCatecholamine‐derived alkaloids of the simple tetrahydroisoquinoline, 1‐benzyltetrahydroisoquinoline and tetrahydroprotoberberine classes have been tested for their ability to inhibit the binding of seven different radioligands to neurotransmitter receptors of brain synaptic membranes. Alkaloids of all three classes were active in inhibiting3H‐clonidine binding to α2‐adrenergic receptors. Stereoselectivity of tetrahydropapaveroline in binding to α2‐adrenergic receptors was evidenced by the marked activity of the S‐(—) isomer (IC50= 0.65 m̈M) in comparison to the R‐(+) enantiomer (IC50= 50 m̈M). The simple tetrahydroisoquinolines (3,4‐dihydroxytetrahydroisoquinoline and salsolinol), the four isomeric mono‐0‐methyl derivatives of 2,3,10,11‐tetrahydroxyberbine and tetrahydropapaveroline were the most potent inhibitors of30H‐apomorphine binding to dopaminergic receptor agonist sites. The tetrahydroprotoberberines, as a class, were the most potent inhibitors of3H‐spiroperidol binding to dopaminergic receptor antagonist sites and of3H‐WB‐4101 binding to α1‐adrenergic receptors. The 1‐benzyltetrahydroisoquinolines exhibited varying degrees of interaction with β1‐adrenergic receptors. Tetrahydropapaveroline (IC50= 0.3 m̈M) was the most active of the 24 alkaloids tested in inhibiting binding of3H‐dihydroalprenolol to β1‐adrenergic receptors. None of the alkaloids significantly affected3H‐QNB binding to muscarinic‐cholinergic receptors, and selected alkaloids from each class i

ISSN:0360-4012    

DOI:10.1002/jnr.490100207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractThe present study reports ultrastructural and biochemical data characteristic of myelin‐related structures in 30‐ to 41‐day‐old cultures of dissociated brain cells from 14‐ to 15‐day‐old embryonic mice. Multilayered membranous material was identified and displayed an alternation of electron‐lucent and electron‐dense lamellae with a periodicity of 102 Å. In these membranes, typical myelin constituents like basic protein, cerebrosides, sulfatides, and CNPase could be identified. Although we are still unable to distinguish if these membranes are premyelin or compact myelin, which could be partly degraded, these results indicate that cultured mouse brain cells retain, to a certain extent, potential to produce myeli

ISSN:0360-4012    

DOI:10.1002/jnr.490100208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractSlices of striatal tissue obtained from saline‐injected rats were incubated with3H‐phenylalanine in the presence of pargyline. This resulted in the formation of3H−m‐tyramine,3H−p‐tyramine, and3H‐phenylethylamine. Pretreatment of the rats with α‐methyl‐p‐tyrosine reduced the formation of3H−m‐tyramine and3H‐p‐tyramine, but enhanced the formation of3H‐phenylethylamine.After incubation of striatal tissue obtained from saline‐injected rats with3H‐ptyrosine, only3H‐p‐tyramine was produced. In this case, α‐methyl‐p‐tyrosine pretreatment enhanced3H‐p‐tyramine formation.Striatal slices incubated with3H‐m‐tyramine or3H‐p‐tyramine did not yield any significant quantity of3H‐phenylethylamine; nor was14C‐phenylethylamine converted to14C‐m‐tyramine or14C‐p‐tyramine. Pretreatment of the rats with the monoamine oxidase inhibitor pargyline did not appreciably affect these findings.After incubation with3H‐dopamine very small quantities of3H‐m‐tyramine and3H‐p‐tyramine were formed, the ratio between them being 7:1.It is concluded that the major biosynthetic route form‐tyramine formation in the rat straitum is by hydroxylation of phenylalanine, probably by tyrosine hydroxylase tom‐tyrosine, followed by decarboxylation, probably by L‐aromatic amino acid decarboxylase, tom‐tyramine.para‐Tyramine is formed by decarbo

ISSN:0360-4012    

DOI:10.1002/jnr.490100209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

摘要:

AbstractPrimary cultures of cells dissociated from embryonic mouse brain were demonstrated to be a useful system for studying cell proliferation and its regulation. Ornithine decarboxylase activity was closely correlated with the rate of DNA and RNA synthesis during cell growth, suggesting that the enzyme is as good an indicator of cell proliferation in these cultures as it is in vivo. Both DNA synthesis and ornithine decarboxylase activity were stimulated by insulin. The enzyme was stimulated five‐ to sixfold by insulin and approximately twofold by butyrate,cis‐retinoic acid, and 12‐O‐tetradecanoylphorbol‐13‐acetate. No effect on the enzyme activity was observed with triiodothyroinine, hydrocortisone, growth hormone, cyclic AMP, or

ISSN:0360-4012    

DOI:10.1002/jnr.490100210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY

ISSN:0360-4012    

DOI:10.1002/jnr.490100211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1983

数据来源: WILEY