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1.
The α2-adrenergic receptor regulation of cyclic adenosine monophosphate (cAMP) accumulation in rat brain slices was examined using a prelabeling technique for measuring second messenger production. The mixed α-adrenergic agonist 6-fluoronorepinephrine, as well as the more selective α2-agonists clonidine and UK-14,304, caused a concentration-dependent inhibition of forskolin-stimulated cAMP accumulation in cerebral cortical slices, whereas phenylephrine, a selective α1-adrenergic agonists,had no inhibitory effect in this system. Moreover, α2-adrenergic receptor antagonists were more potent than α1-adrenergic antagonists in blocking the inhibitory response to UK-14,304. Neither α1-norα2-adrenergic antagonists displayed any inhibitory effect when cAMP accumulation was stimulated by isoproterenol, vasoactive intestinal peptide or 2-chloroadenosine. The results provide further evidence that some α2-adrenergic receptors are negatively coupled to adenylate cyclase in brain, and yield a procedure for studying this phenomenon in intact central nervous system tissue. 相似文献
2.
The chronic feeding of a sweetened condensed milk/corn oil diet (CM diet) to adult male rats produced significant increases in body weight and levels of plasma insulin in 34% of the rats fed this diet with respect to chow-fed controls. Levels of alpha 1-noradrenergic receptor binding were lower (32%) in the hypothalamic ventromedial nucleus (VMN) of only those rats which became obese (DIO rats) with respect to both chow-fed controls and those rats which resisted the development of obesity on the CM diet (DR rats). Also, alpha 1-noradrenergic binding was inversely proportional to body weight gain in the VMN (r = -0.831). alpha 2-Noradrenergic receptors were 30-37% lower in both the DIO and DR rats in the dorsomedial nucleus and dorsal area of the hypothalamus, and the medial dorsal area and nucleus reuniens of the thalamus. The similar decreases in alpha 2-noradrenergic receptors in both the DIO and DR rats in these areas suggested that dietary factors alone were responsible for these changes. There were no significant differences from chow-fed rats for hypothalamic dopamine (D2) or beta-noradrenergic (beta 1- and beta 2-) receptors in either DR or DIO rats. These results indicate that VMN alpha 1-noradrenergic receptors co-vary with body weight and implicate a role for alpha 1-receptors in the VMN in the central neuronal regulation of body weight. 相似文献
3.
4.
The relationship between norepinephrine-stimulated phosphatidyl-inositol metabolism andα1-adrenergic receptor density was examined in rat brain. Increases in phosphatidyl-inositol metabolism were determined by accumulation of [3H]inositol phosphates in the presence of lithium in brain slices, while receptor density was determined by specific binding of125I-BE 2254 (125IBE) in membrane fractions. Treatment of slices of cerebral cortex with increasing concentrations of the irreversibleα1-adrenergic receptor antagonist phenoxybenzamine caused a parallel inactivation of specific125IBE binding sites and norepinephrine-induced [3H]inositol phosphate accumulation, although approximately 20% of the binding sites remained after abolition of the inositol response. Comparison of the density of125IBE binding sites and the magnitude of norepinephrine-stimulated [3H]inositol phosphate accumulation in 8 different brain regions did not show a particularly good correlation. The thalamus had the highest density of binding sites and an intermediate inositol response, while the hippocampus had the highest inositol response but an intermediate density of binding sites. However, the cerebellum had the lowest density of binding sites and no measurable inositol response. Treatment of slices of each region with 300 nM phenoxybenzamine abolished the inositol response and caused a 59–73% decrease in the density of125IBE binding sites. The lack of correlation between receptor density and inositol response between brain regions could not be explained on the basis of receptor affinity, spare receptors, protein content, nor differences in slice size. These results suggest thatα1-adrenergic receptors labeled by125IBE are coupled to [3H]inositol metabolism in rat brain, but the receptor density is not the sole determinant of the magnitude of norepinephrine-induced increases in [3H]inositol metabolism. 相似文献
5.
Tritium-sensitive film autoradiography was used to determine the distribution of α-noradrenergic receptors (i.e. [3H] p-aminoclonidine binding sites) in guinea pig forebrain. α2-Receptors are heterogeneously distributed throughout the forebrain. Many limbic system structures, such as bed nucleus of stria terminalis, medial preoptic area, medial amygdaloid nucleus and lacunosum molecular layer in hippocampus were heavily labeled. We did not quantify receptor density in areas containing principally white matter but the optical density in those areas was similar to film background suggesting a very low receptor density. Low receptor concentrations were also found in areas that do not contain a high percentage of white matter, such as lateral septum and ventromedial hypothalamic nucleus. 相似文献
6.
The agonist specificity pattern of the β-adrenergic adenylate cyclase in glial primary cultures was not typical of either β1- or β2-adrenergic receptors. The dose-response curves for adrenaline did not correspond to simple mass action kinetics and their computer analysis suggests the presence of both β1- and β2-adrenergic-sensitive adenylate cyclase (58 ± 17% and 42 ± 17% respectively).Similar properties of β1- and β2-adrenergic-sensitive adenylate cyclases were found by computer analysis of the dose-response curves for isoprenaline in the presence of a constant concentration of practolol (a selective β1 antagonist) ( 55 ± 10% and 45 ± 10% of β1- and β2-sensitive adenylate cyclase respectively).The curves for displacement of [3H]dihydroalprenolol by practolol confirm these results.For purpose of comparison, the β-adrenergic receptors of meningeal cells in cultures were subjected to similar analysis. The results clearly showed that these cells exclusively contained β2-adrenergic receptors. 相似文献
7.
J.A. Court E.K. Perry D. Spurden S. Lloyd J.I. Gillespie P. Whiting R. Barlow 《Brain research》1994,667(1)
(−)-Nicotine, cytisine and carbachol evoked86Rb efflux from mouse fibroblasts stably transfected with α4β2 chick brain nicotinic subunits. This response to (−)-nicotine was inhibited by mecamylamine and dihydro-β-erythroidine and was mirrored by a rise in intracellular Ca2+ measured by microspectrofluorimetry. Lobeline and isoarecolone methiodide evoked no significant86Rb from cells and unlike the above agonists displayed significantly different IC50 values for the displacement of [3H]nicotine from mammalian (rat and human cerebral cortex) and transfected fibroblast membranes. 相似文献
8.
The actions of the diterpene forskolin, and cyclic AMP analogues, on the evoked release of [3H]GABA (γ-aminobutyric acid) was examined in intact striatal neurons in primary culture, generated from the fetal mouse brain. Exposure of striatal neurons to forskolin (100 μM) resulted in a 40–55% attenuation of [3H]GABA release evoked by either KCl (30 mM) or veratrine (2 μg/ml), while baseline levels of release were unaffected. The dose-dependence for forskolin in striatal neurons. Exposure of striatal neurons to membrane-permeable identical to the dose-dependent elevation of cyclic AMP levels by forskolin in striatal neurons. Exposure of striatal neurons to membrane-permeable analogues of cyclic AMP, such as p-chlorophenylthio cyclic AMP (0.5 mM) and dibutyryl cyclic AMP (1 mM), resulted in a 25 and 26% attenuation of [3H]GABA release, respectively; dibutyryl cyclic GMP (1 mM) was without effect. The similarity between the actions of forskolin and the cyclic AMP analogues suggests that, in striatal neurons in primary culture, the elevation of cyclic AMP levels results in the attenuation of the evoked release of [3H]GABA. The greater effectiveness of forskolin, compared to the cyclic AMP analogues, may be related to the recently reported, additional direct actions of forskolin on neuronal membrane ion channels. 相似文献
9.
In this experiment, we examined the influence of estradiol on α2-noradrenergic receptor binding in the female guinea pig brain with tritium-sensitive film autoradiography. Treatment of ovariectomized guinea pigs with estradiol increased α2-receptor binding in regions of the preoptic area and decreased binding in the ventromedial nucleus of the hypothalamus. There was no effect of estradiol on α2-receptor concentrations in other estradiol concentrating regions or in brain areas which do not concentrate estradiol. 相似文献
10.
Changes in brain α-adrenoceptors with increasing age in rabbits 总被引:2,自引:0,他引:2
The effects of aging on rabbit brain alpha-adrenoceptor number was studied using radioligand binding techniques. The ligands [3H]prazosin and [3H]clonidine were used to examine binding to alpha 1 and alpha 2-adrenoceptors, respectively, in forebrain and hindbrain membranes from rabbits aged from 1 month to 3 years. Changes in specific [3H]clonidine binding were compared to changes in central alpha 2-adrenoceptor function as measured by the fall in blood pressure after intracisternal administration of clonidine. Both alpha 1- and alpha 2-adrenoceptor number decreased with age in the rabbit brain. The maximum fall in specific [3H]prazosin binding occurred in animals aged between 3 and 6 months. [3H]clonidine binding in forebrain was also reduced in 6-month-old animals but [3H]clonidine binding in hindbrain was only reduced in animals over 2 years old. Despite the reduction in [3H]clonidine binding no decrease in the in vivo response to centrally administered clonidine was observed in 2-year-old animals when compared to 3-month-old rabbits. 相似文献
11.
To explore the role of α2-macroglobulin receptor/low density lipoprotein receptor-related protein (α2M-R/LRP) and its ligands in the pathogenesis of Alzheimer's disease (AD), antibodies were raised against its α- and β-subunits and their expression pattern in the CNS in AD and control cases was correlated with that of native and transformed α2-macroglobulin (α2M) and interleukin 6 (IL-6). The transmembranous β-subunit of α2M-R/LRP and transformed α2M were found in plaque cores in AD. Extramembranous α-subunit and native α2M immunoreactivities were localized in activated plaque-associated astrocytes and extracellulary in plaques. IL-6 immunostaining was associated with neurofibrillary changes, and was also found extracellularly in the center of plaques and in microglial cells. Our finding that plaque cores contain a second transmembranous protein fragment, the β-subunit of α2M-R/LRP, suggests ongoing membrane-protein degradation. By altering clearance and scavenger-like functions, fragmentation and breakdown of α2M-R/LRP may have an important role in extracellular amyloid deposition and the formation of neurofibrillary tangles in AD. 相似文献
12.
In the present study we examined the distribution of α2A- and α2C-adrenoceptors in tissue slices from the rat cervical spinal cord and from brain slices collected at the level of the striatum. To differentiate between α2A- and α2C-adrenoceptors, the slices were incubated with [3H]MK912 in the presence of graded concentrations of the α2A-selective drug, BRL44408, or the α2C-selective drug, spiroxatrine. Computer analysis of the autoradiograms indicated that 0.4 nM [3H]MK912 plus 185 nM BRL44408 selectively labeled α2C-adrenoceptors, while 0.4 nM [3H]MK912 plus 220 nM spiroxatrine selectively labeled α2A-adrenoceptors. Using this approach, α2C-adrenoceptors were detected in the striatum, while α2A-adrenoceptors predominated in the cortical layers 1–4, the spinal cord distal dorsal horn, the septum and the endopiriform nucleus. 相似文献
13.
C. Fabrizi M. Colasanti T. Persichini R. Businaro G. Starace G.M. Lauro 《Journal of neuroimmunology》1994,53(1)
An established human astrocytoma cell line (T67) was shown to constitutively produce the proteinase inhibitor α2macroglobulin (α2M). Interferon gamma (IFNγ), a potent immunoregulatory lymphokine, was able to increase the synthesis of α2M by these cells, as measured by ELISA on cell supernatants. The α2M induction was also observed in other human glioma cell lines (T70 and ADF) and in human fetal astrocyte cultures following IFNγ treatment. In T67 cells this effect was dose-dependent and the maximum (2.7-fold increase) was obtained with 2000 U/ml of IFNγ. A corresponding enhanced α2M mRNA accumulation was demonstrated by PCR and Northern blot techniques. Our results suggest an important role of α2M during inflammatory and immune processes in the CNS. An increased release of α2M following IFNγ stimulation may allow the removal of the bulk of proteases released at the site of inflammation, strengthening at the same time the antigen presentation processes. 相似文献
14.
T. Nakamura M. Yoshimura P. Shinnick-Gallagher J.P. Gallagher T. Akasu 《Brain research》1984,323(2):349-353
We used intracellular recording methods to analyze the membrane responses to norepinephrine in cat vesical parasympathetic ganglia. In parasympathetic neurons, norepinephrine (NE) produces a membrane hyperpolarization, a membrane depolarization often accompanied by cell firing and a biphasic potential, a hyperpolarization followed by a depolarization. We found that the NE hyperpolarization is mediated through alpha 2-adrenoceptors while the NE depolarization is mediated through alpha 1-adrenoceptors. This situation is different than in sympathetic neurons where beta-adrenoceptors mediate a NE depolarization. 相似文献
15.
Marie Bixo Agneta Andersson Bengt Winblad Robert H. Purdy Torbjrn Bckstrm 《Brain research》1997,764(1-2)
Post-mortem concentrations of progesterone, 5α-pregnane-3,20-dione (5α-DHP) and 3α-hydroxy-5α-pregnane-20-one (allopregnanolone) were measured in 17 brain areas and serum in five fertile and five postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of all three steroids. The highest progesterone levels were noted in the amygdala, cerebellum and hypothalamus and the highest levels of 5α-DHP and allopregnanolone were seen in the substantia nigra and basal hypothalamus. Brain concentrations of all three steroids were significantly higher in the fertile women in luteal phase compared to their postmenopausal controls (P<0.01). In general, the study showed that there is a variation in brain concentrations depending on ovarian steroid production, indicating that the secretion pattern during the menstrual cycle is reflected in the brain. However, regional differences in brain steroid levels imply local mechanisms for steroid uptake and binding as well. Investigations of gonadal steroid distributions in the human brain might be of importance considering the actions of these steroids in the central nervous system. Such studies could provide information about physiological mechanisms, such as the ovulation, and also form a baseline for comparative studies of normal and pathological conditions involving steroids, for instance, catamenial epilepsy and the premenstrual tension syndrome. 相似文献
16.
α1- and α2-adrenoceptors were assessed by binding studies using [3H]prazosin and [3H]p-aminoclonidine as ligands in membrane preparations from the cortex, hippocampus and hypothalamus of rats, 3 weeks after intracerebroventricular injection of the neurotoxin 5,7-dihydroxytryptamine. Cortical α1 and hippocampal α2 adrenoceptors were significantly increased. Treatment also affected the affinity of cortical α2 adrenoceptors. These results suggest a heterologous, region-specific regulation of both subtypes of central α-adrenergic receptors by serotonin. 相似文献
17.
Idazoxan and brain α2-adrenoceptors in the rabbit 总被引:1,自引:0,他引:1
The effect of intravenous infusion of idazoxan on the depressor response to intracisternal clonidine 1 microgram/kg and on [3H]yohimbine binding in the fore- and hindbrain of the rabbit was examined. Idazoxan was infused either acutely (30 min) or chronically (5 days) at doses of 0.56 or 1.1 mg/h. Idazoxan 1.1 mg/h reduced the fall in blood pressure after clonidine. This attenuation of the depressor response was observed in the groups that were given the higher dose of idazoxan both acutely and chronically. The extent of attenuation was not modified by the duration of treatment. The low dose of idazoxan given acutely had no significant effect on the response to clonidine but the chronically infused group showed an enhanced response. A significant increase in the number of [3H]yohimbine binding sites (83%) was observed in the forebrain after 5 days infusion of 1.1 mg/h idazoxan with no change in the hindbrain. The lower dose of infusion did not cause any significant change in [3H]yohimbine binding in either brain region. Thus it appears that the susceptibility of the alpha 2-adrenoceptor binding sites to up-regulation by idazoxan may depend on the brain region observed. 相似文献
18.
A 6-hydroxydopamine-induced lesion of the dorsal noradrenergic bundle (DNB) in rats markedly decreased neocortical noradrenaline concentration (NNC) by 72–100% as measured 1, 3 and 13 months after the lesioning procedure. The concomitant assessment of neocortical α2- and β1-adrenoceptor binding (NAAB and NBAB, respectively) usually indicated significant increases of 25–74% for these two variables. There were, however, cases of unchanged NAAB and NBAB which presumably reflected an incomplete DNB lesion and a consequent time-related, partial recovery of NNC. The results emphasize the potential for long-term sequelae of the DNB lesion, and the existence of a critical NNC threshold (10–30% of control NNC values) which modulates postsynaptic α2 and β1-adrenoceptor density. 相似文献
19.
The distribution of alpha-1 and beta-1 adrenoceptors has been studied in the midbrain and forebrain of normal and reeler mutant mice, using autoradiographic visualization of radioiodinated HEAT and ICYP, respectively. All cortical structures and nuclear groups of the murine forebrain and midbrain bind ICYP and HEAT. For each ligand, there is substantial regional variation in binding density and these variations tend to observe boundaries between nuclei or cortical regions or the stratification of cortical regions. Regional variations in binding densities are generally different for ICYP and HEAT. Binding sites for ICYP are distributed densely throughout all fields of the neocortex (particularl, layersI–III > VI) and paleocortex, the striatum, pallidum, substantia nigra and superficial strata of the superior colliculus. Dense concentrations of binding sites for HEAT in cortical structures, by contrast, are limited to frontal (all layers except IV) and anterior cingulate regions of the neocortex and, as with ICYP, the stratum lacunosum-moleculaire of the regio superior of the hippocampal formation. In subcortical structures, again in contrast to the pattern with ICYP, binding density is greatest in the principal nuclei of the dorsal thalamus and the septal nuclei. the regional binding patterns of both ICYP and HEAT in the reeler brain are identical to those in the normal animal. Differential laminar binding patterns within the neocortex are approximately inverted in the two genotypes, however. Thus, binding of ICYP is densest in an inner zone of the mutant, but in the outer 3 layers of the normal neocortex. Binding of this ligand is of relatively lower density in an outer zone of the mutant and in the inner 3 layers of the normal neocortex. Similar inversions are characteristics of the laminar binding patterns of HEAT in the frontal, primary sensory and associational cortical regions of the two genotypes where densest binding is encountered superficially in reeler but at deeper levels of the normal neocortex. 相似文献
20.
The neurite promoting factors in the astroglial conditioned medium (As-CM) were characterized by using primary cultures of embryonic rat neocortical neurons. The factors in the As-CM bind to lectins such as wheat germ agglutinin (WGA), suggesting that they contain sugar moieties. When the WGA-bound fractions were applied on a Superose 6 column, the activity was recovered mainly in two fractions, peak I and peak II. The peak II fraction was further purified by Mono Q anion exchange chromatography. A single protein band of 180 kDa was detected in the final Mono Q fraction by sodium dodesylsulfate polyacrylamide gel electrophoresis. The molecular weight coincided with that ofα2-macroglobulin (α2M). Western blotting showed that the single protein band was reacted with anti-α2M antibody but not with anti-fibronectin and anti-laminin antisera. The neurite-promoting activity of the Mono Q fraction was inhibited by anti-α2M antibody. Furthermore, commercially available α2M also promotes neurite outgrowth in our assay system. These results strongly suggested that α2M is one of the neurite-promoting factors in the As-CM. 相似文献