摘要:

Abstract:Intracerebroventricular injections of angiotensin II caused 108, 62, and 54% increases in monoamine oxidase A activities in rat hippocampus, hypothalamus, and striatum respectively. These activatory effects were abolished by simultaneous injections of eledoisin. No significant changes of monoamine oxidase B activities were found under the same experimental conditions. Neither angiotensin II nor eledoisin changed substrate/inhibitor affinities of both isoenzymes. These data indicate that angiotensin II and tachykinin transmitter systems may exert opposite, long‐term regulatory effects on monoaminergic neurons in rat brai

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01984.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:A single intraventricular injection of tetanus toxin produced a time‐dependent elevation of serotonin levels in brain and spinal cord of adult rats. This tetanus toxin‐induced increase was produced in areas of high density of serotonergic innervation, such as the hypothalamus, hippocampus, and spinal cord. Little or no effect was found in the thalamus, cerebellum, and frontal cortex, areas that are poorly innervated by serotonergic terminals. The responses of catechol‐amines (no change in dopamine level and generalized decrease in norepinephrine) pointed to a specific action of tetanus toxin on the serotonergic system. Stereotaxic injections of tetanus toxin in dorsal or magnus raphe nuclei did not have an evident effect on biogenic amine levels in the brain and spinal cord, respectively. Because direct stereotaxic injections of the toxin in the hypothalamus or hippocampus produced significant serotonin increases in both areas, it is proposed that tetanus toxin interacts with presynaptic targets to produce serotonin accumulation; this is probably due in part to an activation of tryptophan 5‐hydr

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01985.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:The 29‐amino‐acid peptide galanin (GAL) caused concentration‐dependent inhibition of the accumulation of3H‐inositol phosphates (3H‐InsPs) induced by the muscarinic agonist carbachol (CARB; 10‐3‐10‐5M) in the presence of 5 mMlithium, specifically in tissue miniprisms from rat ventral hippocampus. The inhibitory effect of GAL involved the mono‐, bis‐, tris‐, and tetrakisphosphates formed during activation for 2 min of phospholipase C by CARB (1 mM) in the absence of lithium. GAL (1 μM) did not affect α‐adrenergic or serotonergic type 2 receptor‐mediated phosphoinositide (PI) breakdown in the same tissue. GAL by itself neither acted on basal levels of3H‐InsPs nor affected muscarinic receptors in binding studies. Blockade of the T‐, N‐, and L‐types of voltage‐sensitive calcium channel (VSCC) with 200 μMCd2+reduced muscarinic receptor‐mediated PI breakdown by 50% and abolished the inhibitory effect of GAL (1 μM). Reduction of the extracellular Ca2+concentration from 1.3 mMto 0.49 μMabolished the GAL inhibition of CARB‐stimulated PI hydrolysis. Ca2+influx promoted by 18 mMK+depolarization or by 1 μMBay K 8644, a selective agonist of the L‐type VSCC, prevented the inhibitory effect of GAL. Blockade of the L‐type VSCC with nifedipine (1 μM) potentiated the inhibitory effects of GAL without affecting muscarinic stimulation of PI breakdown. The neurotoxin ω‐conotoxin (2 μM), a blocker of both L‐ and N‐types of VSCC, by itself reduced CARB‐mediated breakdown of PIs by ∼25%, and when it was added before GAL (1 μM) there was no summation of the two individual inhibitory effects, a result suggesting a common site of action for GAL and ω‐conotoxin. The data presented thus indicate that GAL modulation of muscarinic stimulation of the phospholipase C activity is mediated b

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01986.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:The effect of the anxiogenic β‐carboline methyl‐β‐carboline‐3‐carboxyamide (FG 7142) on dopamine release in prefrontal cortex and striatum in the awake freely moving rat was determined using the technique of microdialysis. FG 7142 (25 mg/kg, i.p.) caused a time‐dependent increase in dopamine release in prefrontal cortex which was statistically significantly greater than the response to vehicle administration. Dopamine release in striatum was unaltered by FG 7142. Pretreatment of animals with the benzodiazepine antagonist Ro 15‐1788 (30 mg/kg, i.p., 15 min prior to FG 7142 administration) completely abolished the increase in dopamine release caused by FG 7142 in prefrontal cortex. These data indicate that the anxiogenic benzodiazepine inverse agonist FG 7142 can selectively increase dopamine release in prefrontal cortex, and that this effect appears to be mediated via the γ‐aminobutyric acid/benzodiazepin

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01987.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:Effects of the inorganic calcium channel blockers zinc, manganese, cadmium, and nickel on secretion of catecholamines from the perfused adrenal gland of the rat were investigated. Secretion of catecholamines evoked by splanchnic nerve stimulation (1 and 10 Hz) was not affected by nickel (100 μM), partially blocked (50%) by cadmium (100 μM), and almost completely blocked (90%) by zinc (1 mM) or manganese (2 mM). A combination of nickel and cadmium inhibited nerve stimulation‐evoked secretion by 80–90%. Catecholamine secretion evoked by direct stimulation of chromaffin cells by acetylcholine (50 μg), nicotine (5 μM), muscarine (50 μg), and K+(17.5 mM) was not blocked by either cadmium, nickel, or their combination. However, zinc and manganese almost abolished nicotine‐and K+‐evoked secretion of catecholamines. None of the above agents had any effect on the secretion evoked by muscarine. Acetylcholine‐evoked secretion of catecholamines was only partially reduced (50%) by zinc and manganese. We draw the following conclusions from the above findings: (a) cadmium plus nickel selectively blocks the calcium channels of splanchnic neurons but has no effect on calcium channels of the chromaffin cells; (b) zinc and manganese do not discriminate between calcium channels of neurons and calcium channels of chromaffin cells; (c) partial inhibition of acetyl‐choline‐evoked secretion by inorganic calcium channel blockers is consistent with the idea that activation of nicotinic receptors increases Ca2+influx, and activation of muscarinic receptors mobilizes intracellularly bound Ca2+, which is not affected by calciu

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01988.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:Primary cultures of meningeal cells from embryonic rat cerebra secrete neurite growth‐inducing components into serum‐free culture medium. This conditioned medium (CM) was analyzed by FPLC and immunochemical and enzymatic treatments and tested for neurite promoting activity (NPA) in a quantitative bioassay using hippocampal neurons from embryonic rat. By immunoprecipitation or specific adsorption we identified laminin (LN)‐proteoglycan complexes and fibronectin (FN), respectively, as the major neurite promoting components within meningeal cell CM. The LN‐proteoglycan complexes and their NPA were sensitive to chondroitinase (chondroitin ABC lyase, EC 4.2.2.4) and to a smaller extent to heparitinase (heparitin sulfate lyase, EC 4.2.2.8). Minor fractions of the total NPA in CM correlated with free LN and a putative but not yet characterized FN‐proteoglyca

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01989.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:The release of endogenous histamine (HA) from the hypothalamus of anesthetized rats was measured by in vivo microdialysis coupled with HPLC with fluorescence detection. Freshly prepared Ringer's solution was perfused at a rate of 1 μl/min immediately after insertion of a dialysis probe into the medial hypothalamus, and brain perfusates were collected every 30 min into microtubes containing 0.2Mperchloric acid. The basal HA output was almost constant between 30 min and 7 h after the start of perfusion, with the mean value being 7.1 pg/30 min. Thus, the extracellular HA concentration was assumed to be 7.8 nM, by a calculation from in vitro recovery through the dialysis membrane. Perfusion with a high K+(100 mM)‐containing medium increased the HA output by 170% in the presence of Ca2+. Systemic administration of either thioperamide (5 mg/kg, i.p.), a selective H3receptor antagonist, or metoprine (10 mg/kg, i.p.), an inhibitor of HA‐N‐methyltransferase, caused an approximately twofold increase in the HA output 30–60 min after treatment. The combined treatment with thioperamide and metoprine produced a marked increase (650%) in the HA output. The HA output decreased by ∼70% 4–5 h after treatment with α‐fluoromethylhistidine (α‐FMH; 100 mg/kg, i.p.), an inhibitor of histidine decarboxylase. Furthermore, the effect of combined treatment with thioperamide and metoprine was no longer observed in α‐FMH‐treated rats. These results suggest that both HA‐N‐methyltransferase and H3autoreceptors are involved in maintaining a constant level of extracellular HA and that their blockade effectively results in a higher activity level of the endogenous hist

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01990.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:The pharmacological study of the blood‐brain barrier has often been hampered by the unavailability of a large number of pure and fully differentiated brain capillary endothelial cells. Here we describe a homogeneous culture of brain capillary endothelial cells isolated from bovine brain (BBECs), which retain at least some phenotypic characteristics of the functional blood‐brain barrier: intercellular tight junctions and monoamine oxidase activity. These cells were subcultured in vitro, in the absence of any neuronal or glial influences, for>100 doublings without any sign of senescence. The present study is focused on the expression of ß‐adrenergic receptors on BBECs. By Northern blot hybridization, subtype‐specific ligand binding, and cyclic AMP accumulation experiments, we demonstrate that ß1‐ and ß2‐adrenergic receptors are coexpressed (in the respective proportions of 42 and 58%) on BBEC membranes and are functionally coupled to adenylate cyclase. This is the first report documenting a significant number of ß1‐adrenergic receptors on brain capillary endothelial cells. The results are discussed in light of the known noradrenergic innervation of

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01991.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:Monoclonal antibody BM88 recognizes a neuronspecific surface antigen in the CNS and the PNS. In the present study, the antigen recognized by BM88 was immunopurified from pig brain and shown to be a 22‐kDa polypeptide by reducing sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Under nonreducing conditions a protein of 40 kDa was obtained, a result indicating that the antigen is composed of two polypeptide chains of equal molecular weight linked by disulfide bridges. Gel filtration of the purified antigen in the presence of Emulphogene suggested that it may be either a monomeric or a dimeric protein. However, in the presence of Triton X‐100 a monomeric structure was implied.N‐Glycanase digestion indicated that the protein is probably not glycosylated. The purified antigen was characterized as an integral membrane protein by hydrophobic chromatography and phase‐separation experiments with Triton X‐114. The antigen, or at least the antibody binding region of the molecule, is very susceptible to protease attack, as judged by protease digestion experiments on brain membranes. By using very low concentrations of papain combined with short incubation times, the antigen was converted to a 16.3‐kDa membrane‐associated polypeptide as assessed by immunoblotting. This polypeptide contained the BM88 binding epitope. Soluble BM88 immunoreactive polypeptides were not obtained.Bacillus cereusphospholipase C was also unable to solubilize the antigen from the membrane. Our results suggest that the molecule, possessing at least one small extramembranous domain, is attached to the membrane via a po

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01992.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:Regional [14C]leucine incorporation into brain proteins was studied in gerbils after global ischemia for 5 min and recirculation times of 45 min to 7 days, using a combination of quantitative autoradiography and biochemical analysis. After recirculation for 45 min, incorporated radioactivity was reduced to ∼20–40% of control values in all ischemic brain regions. Specific activity of the tracer, in contrast, was increased, a finding indicating that the reduced incorporation of radioactivity was not due to reduced tracer influx from plasma or a dilution of the tracer by increased proteolysis. After recirculation for 6 h, [14C]leucine incorporation returned to control levels in all regions except the CA1 sector of the hippocampus, where it amounted to<50%. After 1 day, protein synthesis in the CA1 sector returned to ∼70% of control values, followed by a secondary decline to<50% after 3 days and returned to near control values after 7 days. Histological evaluations revealed selective neuronal death in the CA1 sector of the hippocampus after 3 days of recirculation. The complex time course of protein synthesis in the CA1 sector suggests a biphasic mode of injury, which may be related to similar changes of calcium homeostasis. The final return to near normal after CA1 neurons have disappeared is explained by astroglial proliferation and demonstrates that at this time protein synthesis is not a marker of neuronal viab

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1991.tb01993.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY