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2.
Clonidine decreases plasma and cerebrospinal fluid arginine vasopressin but not oxytocin in humans 总被引:3,自引:0,他引:3
E R Peskind M A Raskind R D Leake M G Ervin M G Ross D M Dorsa 《Neuroendocrinology》1987,46(5):395-400
To evaluate the alpha 2-noradrenergic regulation of arginine vasopressin (AVP) and oxytocin (OT) in normal humans, we measured the effect of the alpha 2-agonist clonidine on concentrations of these neuropeptides in both plasma and cerebrospinal fluid (CSF). Subjects underwent two lumbar puncture studies, one of which was performed 100 min after oral administration of 5 micrograms/kg clonidine. Plasma AVP and OT were measured at a single time point 10 min before lumbar puncture. Both plasma and CSF AVP were significantly lower in the clonidine condition than in the control (no drug) condition. Neither plasma nor CSF OT differed significantly between conditions. Our data confirm previous reports of alpha 2-noradrenergic inhibition of neurohypophyseal release of AVP into blood, and extend these findings to healthy human subjects. Our data also suggest that AVP appearance in CSF, presumably from extraneurohypophyseal vasopressinergic neurons, is regulated by an inhibitory alpha 2-noradrenergic mechanism. 相似文献
3.
4.
D P Figlewicz D M Dorsa L J Stein D G Baskin T Paquette M R Greenwood S C Woods D Porte 《Endocrinology》1985,117(4):1537-1543
Insulin binding was measured in membrane particles prepared from the liver and several brain regions of 4-month-old female Zucker fa/fa (obese), Fa/fa (heterozygous), and Fa/Fa (lean) rats. High affinity insulin binding was decreased in the olfactory bulb of fatty (0.23 pmol bound/mg protein) and heterozygous (0.16 pmol/mg) rats compared with that in the lean controls (0.64 pmol/mg). Total binding was not changed in the cerebral cortex or hypothalamus. High affinity insulin binding was also decreased in the liver of both fatty (0.44 +/- 0.22 pmol/mg; P less than 0.01) and heterozygous (0.75 +/- 0.35 pmol/mg) animals compared with that in the lean rats (2.10 +/- 1.55 pmol/mg). This decreased binding is probably not due to down-regulation of receptors in the heterozygous rats, as they do not exhibit the hyperinsulinemia observed in the fatty rats. Rather, our findings suggest that there is a gene-related alteration in insulin binding in the Zucker rat, as low binding was observed in rats carrying either one (Fa/fa) or two (fa/fa) doses of the gene. We postulate that this central defect in insulin binding may contribute to inadequate perception of a central insulin feedback signal and to the hyperphagia observed in the obese rats. 相似文献
5.
Distribution of neurotensin/neuromedin N mRNA in rat forebrain: unexpected abundance in hippocampus and subiculum. 总被引:1,自引:0,他引:1
M J Alexander M A Miller D M Dorsa B P Bullock R H Melloni Jr P R Dobner S E Leeman 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(13):5202-5206
We have used in situ hybridization to determine the regional distribution of mRNA encoding the neurotensin/neuromedin N (NT/N) precursor in the forebrain of the adult male rat. Cells containing NT/N mRNA are widely distributed in the forebrain. These areas include the septum, bed nucleus of the stria terminalis, preoptic area, hypothalamus, amygdala, accumbens nucleus, caudate-putamen, and piriform and retrosplenial cortex. In general, the regional distribution of NT/N mRNA corresponds to the previously determined distribution of neurotensin-immunoreactive cell bodies; however, several notable exceptions were observed. The most striking difference occurs specifically in the CA1 region of the hippocampus, where intense labeling is associated with the pyramidal cell layer despite the reported absence of neurotensin-immunoreactive cells in this region. Analysis of microdissected tissue by S1 nuclease protection assay confirmed the abundance of authentic NT/N mRNA in CA1. A second major discrepancy between NT/N mRNA abundance and neurotensin-immunoreactivity occurs in the intensely labeled subiculum, a region that contains only scattered neurotensin-immunoreactive cells in the adult. These results suggest that, in specific regions of the forebrain, NT/N precursor is processed to yield products other than neurotensin. In addition, these results provide an anatomical basis for studying the physiological regulation of NT/N mRNA levels in the forebrain. 相似文献
6.
Yohimbine increases cerebrospinal fluid and plasma norepinephrine but not arginine vasopressin in humans 总被引:1,自引:0,他引:1
Previous studies have demonstrated alpha 2-inhibitory regulation of central nervous system (CNS) noradrenergic and arginine vasopressinergic systems. We tested the hypothesis that alpha 2-inhibition of CNS noradrenergic and vasopressinergic systems is tonic in nature by measuring the response of cerebrospinal fluid (CSF) norepinephrine (NE) and arginine vasopressin (AVP) to the alpha 2-antagonist yohimbine in 7 young normal male human subjects. We also evaluated the tonic nature of alpha 2-inhibition of the sympathetic nervous system (SNS) and of AVP release into plasma by measuring the response of plasma NE and plasma AVP to yohimbine. CSF NE was significantly higher following yohimbine as compared to placebo. In contrast CSF AVP did not differ between yohimbine and placebo conditions. Similarly, plasma NE was significantly higher following yohimbine as compared to placebo, while plasma AVP was unchanged. These results support a tonic alpha 2-inhibitory regulatory mechanism for both CNS noradrenergic systems and sympathetic outflow. Such tonic alpha 2-inhibition could not be demonstrated for regulation of AVP levels in CSF or plasma in humans. 相似文献
7.
The influence of aging on the molecular forms of endorphins in the hypothalamus of rats was investigated. Extracts of individual hypothalami from 8- and 24-month-old male Fischer 344 rats were subjected to high-performance liquid chromatography. Eluate fractions were assayed for beta-endorphin-like immunoreactivity (beta E-LI) and gamma-endorphin-like immunoreactivity (gamma E-LI). Hypothalami from adult (8-month-old) rats contained predominantly beta-endorphin-1-31 with smaller amounts of beta-endorphin-1-27 and 1-26. Only 5% of the beta E-LI co-eluted with alpha-N-acetylated forms of beta-endorphin. In hypothalamic extracts from old rats more than 30% of the beta E-LI co-eluted with acetylated forms of beta-endorphin and over 35% of the beta E-LI co-eluted with acetylated or unacetylated beta-endorphin-1-26. The individual elution profiles of beta E-LI were also much more variable among the old rats than among the adult rats. More than 80% of the gamma E-LI from adult rat extracts co-eluted with gamma-endorphin (beta-endorphin-1-17) and less than 3% with alpha-N-acetyl-gamma-endorphin. In contrast, more than 35% of the gamma E-LI from old rat hypothalami was present in the acetylated form. These results suggest that significant alterations in post-translational processing of peptides may occur in neuropeptide systems during aging. 相似文献
8.
Vasopressin (AVP)-immunoreactive cells have been previously reported in the medial amygdala (AME) and in the locus coeruleus (LC). The present study was designed to verify the presence of AVP-synthesizing neurons in these areas using in situ hybridization histochemistry. A 35S-labelled oligonucleotide probe, complementary to the glycopeptide portion of the vasopressin-encoding mRNA, was used to label cells expressing the AVP gene in brain sections from male Wistar rats. AVP mRNA-positive cells were identified in the AME and were located throughout the anterodorsal and posterodorsal aspect of the nucleus. Cells in the LC, however, did not exhibit labelling for the glycopeptide portion of the AVP gene. The highest density of labelled cells in the medial amygdala occurred 2.30 to 2.80 mm caudal to bregma. The labelling intensity of the cells averaged 53.8 +/- 3.9 grains/cells and was constant throughout the rostro-caudal extent of the AME. These data demonstrate the presence of AVP-synthesizing cells in the AME and provide a method for quantifying their activity. In addition, these data suggest that the cells in the LC may not synthesize vasopressin. 相似文献
9.
E H Chartoff R P Ward D M Dorsa 《The Journal of pharmacology and experimental therapeutics》1999,291(2):531-537
Acute blockade of dopamine D(2) receptors by the typical antipsychotic drug haloperidol leads to alterations in neuronal gene expression and behavior. In the dorsolateral striatum, the levels of mRNA for the immediate-early gene c-fos and the neuropeptide gene neurotensin/neuromedin N (NT/N) are significantly increased by haloperidol. An acute behavioral response to haloperidol is catalepsy, considered to be a rodent correlate of some of the immediate extrapyramidal motor side effects seen in humans. Several lines of evidence suggest a link between neurotensin induction in the dorsolateral striatum and catalepsy. We hypothesize that both striatal gene induction and catalepsy elicited by haloperidol arise from the combined effect of excitatory adenosinergic and glutamatergic inputs acting at adenosine A(2A) and N-methyl-D-aspartate (NMDA) receptors, respectively. In agreement with our previous reports, adenosine antagonists reduced haloperidol-induced c-fos and neurotensin gene expression as well as catalepsy. In agreement with other reports, the noncompetitive NMDA receptor antagonist MK-801 also reduced gene expression and catalepsy in response to haloperidol. The competitive NMDA receptor antagonist LY235959 decreased haloperidol-induced catalepsy. We show here that blocking both A(2A) and NMDA receptors simultaneously in conjunction with haloperidol resulted in a combined effect on gene expression and behavior that was greater than that for block of either receptor alone. Both c-fos and NT/N mRNA levels were reduced, and catalepsy was completely abolished. These results indicate that the haloperidol-induced increases in c-fos and NT gene expression in the dorsolateral striatum and catalepsy are driven largely by adenosine and glutamatergic inputs acting at A(2A) and NMDA receptors. 相似文献
10.
Neuronal apoptosis resulting from high doses of the isoflavone genistein: role for calcium and p42/44 mitogen-activated protein kinase 总被引:1,自引:0,他引:1
Linford NJ Yang Y Cook DG Dorsa DM 《The Journal of pharmacology and experimental therapeutics》2001,299(1):67-75
Genistein is a potent plant-derived isoflavone displaying estrogenic activity at low (nanomolar) concentrations and antiproliferative and antiangiogenic properties at higher concentrations (above 10-50 microM). The antiproliferative potential of genistein has made it an interesting candidate for cancer chemotherapy at high concentrations; however, the potential for genistein toxicity in neurons at such concentrations has not been previously addressed. We show that genistein is toxic to rat primary cortical neurons at a concentration of 50 microM, whereas daidzein, a structural analog, shows no toxicity at similar concentrations. The dying cells display an apoptotic morphology that is characterized by fragmented nuclei, appearance of apoptotic bodies, DNA laddering, and caspase-dependent poly(ADP-ribose) polymerase cleavage. This cell death is partially dependent on caspase activity, independent of estrogen receptors, and does not result in a significant loss of Bcl-2 or Bcl-X(L) protein. Genistein exposure induces delayed and prolonged activation of p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK but not c-Jun NH2-terminal kinase. The specific p42/44 MAPK kinase inhibitor PD98059 (50 microM) partially blocks genistein-induced apoptosis, whereas the p38 MAPK inhibitor SB202190 (10 microM) has no effect. Genistein elevates intracellular calcium and both 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (1 microM) and dantrolene (10 microM) inhibit genistein-induced apoptosis, suggesting a link between genistein-induced intracellular calcium release and apoptosis. The combination of dantrolene and PD98059 block genistein-induced apoptosis in an additive manner compared with either compound alone. These findings provide evidence for a proapoptotic function of p42/44 MAPK and raise caution about potential side effects in the nervous system with genistein use as a high-dose therapeutic agent. 相似文献