ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05618.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Samples of brain anterior temporal cortex from 17 patients with Alzheimer's disease and 18 age‐matched controls have been analysed formyo‐inositol and the three phosphoinositides. There was significantly less phosphati‐dylinositol in the Alzheimer samples (1.36 μmol/g wet weight) than in the controls (2.28 μmol/g). The concentrations of phosphatidylinositol 4‐phosphate and phosphati‐dylinositol 4,5‐bisphosphate were also lower in Alzheimer cortex, but differences from the control group were not statistically significant. Freemyo‐inositol concentrations were 5.11 μmol/g(Alzheimer) and 4.44 μmol/g (control) and again the difference was not significant. The lack of phosphoinositides in Alzheimer temporal cortex may impair

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05619.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Immunoblots of the soluble proteins from a rat brain high‐speed supernatant dissociated under reducing conditions showed two monomers (molecular weights, 59,000 and 62,000 ± 2,000) immunolabeled by a glutamic acid decarboxylase (GAD) antiserum. In this extract, a GAD monoclonal antibody trapped the same two monomers, thus confirming that they are both constitutive sub‐units of GAD. Without treatment under reducing conditions, two additional bands were stained by immunoblotting. Their molecular weights were estimated to be 115,000 and 122,000 ± 5,000. These results demonstrate the presence, in rat brain soluble extract, of two distinct forms of native GAD. They further support our previous hypothesis that each form is composed by the homodimeric association of each constitutive subunit through disulfide br

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05620.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The distribution of thyrotrophin‐releasing hormone (TRH), substance P, and the indoleamines [5‐hy‐droxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA)] has been examined in selected regions of the thoracic and lumbar spinal cord of the rabbit using sensitive radioimmunoassays for the first two and HPLC with electrochemical detection for the indoleamines. The levels of TRH‐ and substance P‐like immunoreactivity (TRH‐I and SP‐I, respectively) were greatest in the ventral and dorsal grey matter, respectively. The level of TRH‐I in most thoracic regions was greater than that in equivalent lumbar regions, but the only segmental difference in SP‐I was in the ventral grey matter, where the lumbar segment contained more immunoreactivity. 5‐HT and 5‐HIAA were more evenly distributed than either peptide and showed no segmental variation in levels in equivalent regions, but the ventral grey matter contained significantly higher levels of 5‐HT and had a greater 5‐HT/5‐HIAA ratio than all other regions. The absolute levels and the overall distribution of SP‐I, TRH‐I, and indoleamines in the thoracolumbar cord of the rabbit was very similar to that previously reported in both rats and humans, and the possible functional role of the peptides and indolea

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05621.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Phosphatidylinositol phosphodiesterase (PL‐C) appears to be a key element in the adrenergic regulation of pineal cyclic AMP levels. In the present study, the rat pineal enzyme was characterized using exogenous [3H]phosphati‐dylinositol (0.5 mM) as substrate. Half the enzyme activity was found in the cytosolic fraction, but the highest specific concentration was associated with the membrane fraction. Two pH optima (5.5 and 7.5) of enzyme activity were observed for the membrane fraction but only one in the cyto‐sol fraction (pH 5.5). Enzyme activity in both fractions was Ca2+dependent. In the case of the membrane protein in pH 7.5, the enzyme activity was sensitive to changes in Ca2+in the 10–100 nAf range. Addition of an equimolar concentration of phosphatidylinositol 4‐phosphate nearly completely inhibited the hydrolysis of [3H]phosphatidylinositol; other phospholipids (1.0 mM) were less potent. This may reflect our present finding that [3H]phosphatidylinositol 4‐phosphate is a better substrate than [3H]phosphatidylinositol for the enzyme. Stimulus deprivation (2 weeks of constant light or superior cervical ganglionectomy) reduced the cytosolic activity by 30% and had no effect on the membrane‐asso

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05622.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:A series of l‐phenyl‐1H‐3‐benzazepine analogues were assessed for enantiomeric and structure‐affinity relationships at human putamen D‐1 dopamine receptors labelled with [3H]SCH 23390. Substitution at the 7‐position of both 3‐H and 3‐methyl benzazepine molecules critically affected affinity for these receptors over a 500‐fold range. The general rank order of potency of 7‐substituents was Cl = Br ≫ CH3>OH ≥ H. 3‐Methyl substituents increased the affinity of 7‐H and 7‐OH compounds two‐ to fivefold compared to desmethyl counterparts. The displacement of [3H]SCH 23390 binding showed substantial enantioselec‐tivity; the R‐enantiomer of SKF 83566 was 500‐fold more potent that its S‐antipode. However, the displacement of [3H]spiperone binding from D‐2 sites in the same tissue showed negligible enantioselectivity. Through such structure‐affinity relationships, these studies may help to define the topography of the human brain D‐1 dopamine receptor and guide the design

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05623.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Synaptosomes prepared from rat cerebral cortex and labeled with [3H]noradrenaline (NA) were superfused with calcium‐free Krebs‐Ringer‐bicarbonate medium and exposed to 10 mMK+plus 0.1 mMCa2+so that [3H]NA release was induced. 6,7‐Dihydroxy‐N,N‐dimethyl‐2‐ami‐notetralin (TL‐99) strongly inhibited synaptosomal K+‐in‐duced [3H]NA release (EC50= 5–10 nM) by activating α2‐adrenoceptors. Release was also inhibited (maximally by 40–50%) by morphine (EC50= 5–10 nM), [Leu5]enkephalin (EC50=∼300 nM), [d‐Ala2,d‐Leu5]enkephalin (DADLE), and Tyr‐d‐Ala‐Gly‐(NMe)Phe‐Gly‐ol (DAGO) (EC50values =∼30 nM). In contrast to the μ‐selective opioid receptoragonists morphine and DAGO, the highly δ‐selective agon ist [d‐Pen2, dPen5]enkephalin (1 μM) did not affect [3H]‐NA release. Furthermore, the inhibitory effect of DADLE, an agonist with affinity for both δ‐and μ‐opioid receptors, was antagonized by low concentrations of naloxone. The findings strongly support the view that, like α2‐adrenocep‐tors, μ‐opioid receptors mediating inhibition of NA rele

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05624.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Antibodies to Gm1ganglioside enhance the release of γ‐aminobutyric acid (GABA) from rat brain slices induced by depolarization with either 40 mMK+or 200 μMveratrine. Three new observations are now reported, (a) GABA release induced by the Ca2+ionophore A23187 was not affected by these antibodies. Because this Ca2+ionophore causes transmitter release by bypassing depolarization‐induced opening of Ca2+channels, this result suggests that gangliosides participate either in the functioning of such Ca2+channels or in the Na+channels involved in depolarization, (b) The enhancement (by antibodies to GM1ganglioside) of GABA release induced by high K+levels occurred in the presence of tetrodotoxin (0.01 μM). (c) GABA release induced by veratrine in the absence of Ca2+was not affected by the antibodies. These latter two observations indicate that Na+channels are not involved in the action of the antibodies. We conclude that this evidence points to the participation of gangliosides in Ca2+channel functions involved in GABA release in rat brain

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05625.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:At the time of terminal differentiation, mammalian cortical neurons undergo a dramatic change in the structural organization of their chromatin: the nucleosomal repeat length shortens from ∼200 base pairs in fetuses to a value of 165 base pairs after birth. These events occur several days after the end of neuronal proliferation. Previously, we reported that rat cortical neurons cultured in a very selective synthetic medium were not yet programmed to these events at the end of mitotic cycles. Herein, we report that addition of triiodothyronine to neuronal cultures induces a shortening of the chromatin repeat length comparable to the natural on

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05626.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Slices of rat cerebral cortex, preloaded with [14C]γ‐aminobutyric acid (GABA) and either [3H]5‐hy‐droxytryptamine (5‐HT) or [3H]noradrenaline, were super‐fused with media in which varying concentrations of Cl−had been replaced with other monovalent anions. Rapid reduction of [Cl″], by superfusion with media containing instead the impermeant anions propionate, isethionate, glu‐conate, or methyl sulphate, caused increases in the efflux of tritiated biogenic amines, but the increase in that of [14C]‐GABA was not significant. The increased efflux of [3H]5‐HT evoked by superfusion with low Cl−levels when propionate was the replacement anion, was transient and was linearly related to the log[Cl−]−1. It was not affected by removal of Ca2+or by addition of 10 mMMg2+and was delayed but not abolished by tetrodotoxin. The low C1–‐evoked efflux of [3H]5‐HT was not affected by pretreatment with neuronal reuptake blockers but was inhibited by picrotoxin, strychnine, and 4‐acetamido‐4‐isothiocyanostilbene‐2,2‐disul‐phonic acid and was enhanced by glycine. Muscimol and GABA were without effect. These observations are taken to indicate that the efflux of biogenic amines is brought about by terminal depolarisation due to outward movement of Cl−in low chloride‐containing media. They are of relevance to other physiological and pharmacological studies in which anion concentrations are manipulated and suggest that the anion‐evoked release phenomenon may provide a model for the analy

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1987.tb05627.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY