共查询到20条相似文献,搜索用时 15 毫秒
1.
Graciela Piñeyro Lyne Deveault Pierre Blier Trevor Dennis Claude de Montigny 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(2):111-118
In the present study, in vivo extracellular unitary recordings, in vitro [3H]5-HT uptake and [3H]cyanoimipramine binding assays were used to assess the effect of acute and prolonged administration of the putative antidepressant tianeptine, on the 5-hydroxytryptamine (5-HT) transporter. Microiontophoretic application of tianeptine onto dorsal hippocampus CA3 pyramidal neurons, as well as its intravenous administration (2 mg/kg), increased their firing frequency. Following intracerebroventricular administration of 5,7-dihydroxytryptamine, the activation induced by the microiontophoretic application of tianeptine remained unchanged, thus suggesting that the 5-HT carrier is not involved in this effect. Furthermore, in spite of its activating effect on CA3 pyramidal neuron firing frequency, the intravenous administration of tianeptine did not alter the time of recovery of these neurons from microiontophoretic applications of 5-HT, an index of 5-HT uptake activity. In keeping with this observation, the acute administration of tianeptine did not change the effectiveness of the 5-HT reuptake blocker paroxetine (1 mg/kg, i.v.) in prolonging the suppressant effect of microiontophoretically-applied 5-HT. However, in rats that had received tianeptine for 14 days (20 mg/kg/day, s.c.), the recovery time from the suppressant effect of microiontophoretic applications of 5-HT was reduced by 40% and the effectiveness of paroxetine (1 mg/kg, i.v.) was decreased. These effects were no longer observed following a 48 h washout period. In a second series of experiments, the ability of tianeptine to interfere with the uptake blocking capacity of paroxetine was assessed in vitro, using hippocampal slices obtained from rats that had been treated with tianeptine for 14 days (20 mg/kg/day, s.c.; by minipump). The effectiveness of paroxetine to block [3H]5-HT uptake was unchanged in slices obtained from rats still bearing the osmotic minipump at the time of the sacrifice, as well as from those which had undergone a 48 h washout period. To assess whether prolonged administration of tianeptine would induce adaptive changes on 5-HT uptake sites, [3H]cyanoimipramine-binding parameters were measured following a 48 h washout period. Affinity values remained unchanged while density values were significantly increased in cortex (+22%) but not in hippocampus (+12%). It is concluded that, i) the activation of CA3 pyramidal neurons observed following acute tianeptine administration cannot be attributed to its 5-HT uptake enhancing properties and ii) the prolonged administration of tianeptine induces adaptive changes on cortical but not on hippocampal 5-HT transporters.Deceased 10 May 1994 相似文献
2.
A. Newman-Tancredi L. Verrièle C. Chaput M. J. Millan 《Naunyn-Schmiedeberg's archives of pharmacology》1998,357(3):205-217
The novel benzodioxopiperazine, 5-HT1A receptor weak partial agonist, S 15535 (4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine) bound with high affinity and selectivity
to membranes of Chinese Hamster Ovary cells stably expressing the human (h) 5-HT1A receptor (Ki = 0.6 nM versus [3H]-8-hydroxy-dipropylamino-tetralin, [3H]-8-OH-DPAT): its affinity at h5-HT1A receptors was more than 70-fold higher than its affinity at > 50 other binding sites. S 15535 was tritiated to high specific
activity (50 Ci/mmol) and its binding profile characterised. At 22° C, [3H]-S 15535 associated and dissociated from h5-HT1A receptors with half-times of 2.9 and 5.0 min, respectively, yielding a Kd estimate of 3.6 nM. In saturation binding experiments, [3H]-S 15535 displayed a Bmax value for h5-HT1A receptors (1630 fmol/mg), higher than that obtained with the agonist [3H]-8-OH-DPAT (1023 pmol/mg). Guanylyl imidodiphosphate (GppNHp, 100 μM) reduced the binding of [3H]-S 15535 by only 25% compared with 79% for [3H]-8-OH-DPAT at h5-HT1A receptors. [3H]-S 15535 also showed high affinity, saturable binding to rat hippocampal membranes (Bmax = 820 fmol/mg versus 647 fmol/mg for [3H]-8-OH-DPAT). For both h5-HT1A and rat 5-HT1A receptors, the Ki values for competition binding of 15 serotonergic ligands with [3H]-S 15535 was highly correlated with that of [3H]-8-OH-DPAT. However, important differences were also observed. The agonist, 5-hydroxytryptamine (5-HT), displayed biphasic
competition curves with [3H]-S 15535 but not with [3H]-8-OH-DPAT at h5-HT1A receptors. Similarly, the ‘antagonists’, spiperone, methiothepin and (+)butaclamol, showed biphasic competition isotherms
versus [3H]-S 15535 but not [3H]-8-OH-DPAT. When [3H]-S 15535 competition binding experiments were carried out in the presence of GppNHp (100 μM) the 5-HT and 8-OH-DPAT competition
curves shifted to the right, whereas the spiperone and methiothepin competition curves shifted to the left. In contrast, in
the presence of GppNHp, the competition isotherms for N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide
(WAY 100,635) were not altered. Taken together, these data show that (i) [3H]-S 15535 is a highly selective 5-HT1A receptor ligand which labels both G-protein-coupled and uncoupled 5-HT1A receptors, (ii) antagonists, such as WAY 100,635, which yield monophasic isotherms in competition with both [3H]-agonists and [3H]-antagonists, are not sensitive to the G-protein coupling state of the receptor, but (iii) spiperone and methiothepin behaved
as inverse agonists, their competition isotherms with [3H]-S 15535 being modulated in an opposite manner to those of agonists.
Received: 12 September 1997 / Accepted: 1 December 1997 相似文献
3.
Kevin M. Lawrence Jan Falkowski Robin R. Jacobson Roger W. Horton 《Psychopharmacology》1993,110(1-2):235-239
Platelet 5-HT uptake sites were measured in 40 depressed patients and 40 controls using [3H] imipramine binding, defined with desmethylimipramine (DMI) and Na+ dependence, and [3H] paroxetine binding. In control subjects the Bmax of DMI defined [3H] imipramine binding was significantly higher than both Na+ dependent [3H] imipramine (by 30%) and [3H] paroxetine binding (by 22%). The Bmax of Na+ dependent [3H] imipramine and [3H] paroxetine binding did not differ significantly. The Kd of Na+ dependent [3H] imipramine binding was significantly lower than the Kd of DMI defined [3H] imipramine binding. The binding of DMI defined and Na+ dependent [3H] imipramine and [3H] paroxetine did not differ significantly between depressed patients and controls in the total group, in those depressed patients who had never taken antidepressants or in those depressed patients who had been recently with-drawn from antidepressants. This study provides no support for the view that the number of platelet 5-HT uptake sites are reduced in depression. 相似文献
4.
Several reports have shown heterogeneity of [3H]imipramine binding to brain membranes. Recently, a high affinity and 5-HT sensitive [3H]imipramine binding site of protein nature, that was suggested to be identical to the substrate recognition site for 5-HT uptake, was demonstrated. Since most studies on the regulation of the [3H]imipramine binding sites by antidepressants have used desipramine displaceable binding, which is heterogenous in nature and contains binding not related to 5-HT uptake sites, the present report studies the possible effects of chronic (3 weeks) administration of imipramine or norzimeldine (10 mg/kg intraperitoneally twice daily) on 5-HT sensitive [3H]imipramine binding sites. For comparison, desipramine sensitive binding was also studied, as well as the physiological correlate 5-HT uptake. There were no changes in either [3H]imipramine binding or 5-HT uptake after the antidepressant treatment.Supported by the Swedish Medical Research Council
Offprint requests to: J. Marcusson at Dept. of Geriatric Medicine 相似文献
5.
M. Bühlen K. Fink C. Böing M. Göthert 《Naunyn-Schmiedeberg's archives of pharmacology》1996,353(3):281-289
The effects of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on tritium overflow evoked by high K+ were determined in superfused synaptosomes and slices, preincubated with [3H]5-HT, from guinea-pig brain cortex. In addition, we estimated the potencies of 5-HT receptor ligands in inhibiting specific [3H]5-HT binding (in the presence of 8-hydroxy-2(di-n-propylamino)tetralin and mesulergine to prevent binding to 5-HT1A and 5-HT2C sites) to guinea-pig cortical synaptosomes and membranes.5-HT receptor agonists inhibited the K+-evoked tritium overflow from synaptosomes and slices. In synaptosomes the rank order of potencies was 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indole-3-yl] ethylamine (L-694,247) >5-carboxamidotryptamine (5-CT) > oxymetazoline (in the presence of idazoxan) 5-HT > sumatriptan 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969). The potencies of the agonists in inhibiting tritium overflow from slices correlated with those in synaptosomes, suggesting that the same site of action is involved in both preparations. In synaptosomes the nonselective antagonist at cloned human 5-HT1D, and 5-HT1D receptors, methiothepin, shifted the concentration-response curve for 5-CT to the right (apparent pA2: 7.87). In contrast, ketanserin at a concentration which should block the 5-HT1D, but not the 5-HT1D\, receptor did not alter the inhibitory effect of 5-CT on tritium overflow. In cortical synaptosomes and membranes, [3H]5-HT bound to a single site with high affinity. In competition experiments, 5-HT receptor agonists and antagonists inhibited specific [3H]5-HT binding. In synaptosomes the rank order was L-694,247 > methiothepin >5-CT >5-methoxytryptamine >5-HT sumatriptan oxymetazoline > RU 24969 > ketanserin > ritanserin. A very similar rank order was obtained in cerebral cortical membranes. The potencies of the 5-HT receptor agonists in inhibiting tritium overflow from synaptosomes and slices correlated with their potencies in inhibiting [3H]5-HT binding to synaptosomes and membranes.In conclusion, the 5-HT receptors mediating inhibition of 5-HT release in the guinea-pig cortex are located on the serotoninergic axon terminals and, hence, represent presynaptic inhibitory autoreceptors. The [3H]5-HT binding sites in cerebral cortical synaptosomes and membranes exhibit the pharmacological properties of 5-HT1D receptors. The correlation between the functional responses and the binding data confirms the 5-HT1D character of the presynaptic 5-HT autoreceptors. According to the results of the interaction experiment of ketanserin and methiothepin with 5-CT on 5-HT release, the presynaptic 5-HT autoreceptors can be subclassified as 5-HT1D\-like. 相似文献
6.
Kevin M. Lawrence Cornelius L. E. Katona Mohammed T. Abou-Saleh Mary M. Robertson Bertrand L. Nairac Denzil R. L. Edwards Toni Lock Roger A. Burns Deborah A. Harrison Roger W. Horton 《Psychopharmacology》1994,115(1-2):261-264
Platelet [3H] paroxetine binding was measured in 73 depressed patients and in 64 healthy volunteers. No differences were found in Bmax or Kd either overall, or when the 61 depressed subjects who had never received psychotropic drugs were analysed separately. Within the depressed group, no differences in Bmax or Kd were found between subgroups divided on the basis of endogenicity, suicidal thoughts or severity of depression. None of the subgroups differed significantly from controls. Forty of the depressed subjects were retested after 6 weeks' treatment with fluoxetine (n=22) or lofepramine (n=18). Treatment was not associated with any change in Bmax but a similar and significant increase in Kd was noted following treatment with either antidepressant. Neither pre- nor post-treatment platelet binding parameters appeared to relate to clinical response to treatment. 相似文献
7.
Rationale It has been reported that 5-HT1A receptors modulate learning and memory and diverse pharmacological and genetic evidence supports this notion. Nevertheless,
there are few works about expression of these receptors during memory formation.
Objective We aimed to determine 5-HT1A receptor expression in brain areas of untrained, passive, and autoshaping trained groups of rats.
Methods Ex vivo receptor autoradiography using the ligand agonist [3H]8-hydroxy-2-[di-n-propylamino]tetralin] (8-OH-DPAT) was used.
Results The trained group relative to untrained animals showed increases of 5-HT1A receptor expression in 14 brain areas, decrements in 7, and no changes in 12. Thus, in contrast to untrained rats, 5-HT1A receptor expression of autoshaping trained rats was augmented in the tubercule olfactory, septal nucleus, nucleus accumbens,
caudate putamen, globus pallidus, striate, and parietal (1 and 2), temporal cortex (1 and 3), granular retrosplenial cortex
(1), amygdala, and median and dorsal raphe nuclei. In contrast, in the latter group, receptors were decreased in the CA1 area,
hypothalamus dorsal, frontal cortex (1 and 3), occipital cortex, cingulate cortex (1 and 2), and cuneiform nucleus. There
were significant differences between passive vs trained groups, but not regarding untrained rats, in the lateral olfactory
tract, dentate gyrus, CA3 area, ventromedial hypothalamic, lateral hypothalamus, preoptic medial, frontal cortex (2), granular
retrosplenial cortex (2), entorhinal cortex (1 and 2), piriform cortex, and substantia nigra.
Conclusions These data suggest that upregulated, downregulated, and “silence” of 5-HT1A receptors in brain areas form part of neural circuits engaged in memory formation by demonstrating a high degree of specificity
and memory mapping. 相似文献
8.
In the present study, the effect of chronic treatment with venlafaxine on β1 and 5-HT2 receptor populations was examined in the frontal cortex of olfactory bulbectomised (OB) and sham operated (SO) animals. The
effect of these drugs on the behaviour of the animals on the elevated plus maze and the “open field” was also assessed. Removal
of the bulbs resulted in a characteristic increase in locomotor activity in the OB animals in the “open field” which was reversed
by chronic venlafaxine treatment. Venlafaxine produced a slight reduction in the number of open arm entries made by the OB
animals although this failed to reach significance. Maximum change in temperature from baseline, following a single dose of
8-OH-DPAT (1.5 mg kg−1 SC), was used to assess the function of the 5-HT1A receptors. Chronic venlafaxine treatment had no effect on the hypothermic response to 8-OH-DPAT in the present study. A decrease
in the affinity of β1-adrenoceptors was found following olfactory bulbectomy and this was normalised by treatment with venlafaxine. No bulbectomy-induced
changes were evident 32 days post surgery in β1-adrenoceptor density; however, chronic treatment with venlafaxine significantly reduced the density of these receptors in
the OB animals. Olfactory bulbectomy did not produce any changes in 5-HT2 receptor populations but venlafaxine administration significantly reduced the density of these receptors in both SO and OB
animals. The findings of the present study further validate the usefulness of the OB as an animal model, for the detection
of antidepressants from a wide variety of classes.
Received: 22 August 1997/Final version: 11 November 1997 相似文献
9.
Michael P. Johnson Barry W. Siegel Albert A. Carr 《Naunyn-Schmiedeberg's archives of pharmacology》1996,354(2):205-209
In studies using standard radioligands, unlabeled MDL 100,907 (R-(+)--(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol) has been shown to have a high degree of selectivity for the 5-HT2A receptor. The present study was undertaken to investigate the receptor binding characteristics of [3H]MDL 100,907 in rat cortical homogenates. [3H]MDL 100,907 was found to reach equilibrium at 37°C after 15 min. Saturation experiments indicated binding to a single site with a KD of 0.56 nM, Hill slope of 1.15, and a Bmax of 512 fmol/mg protein. In parallel experiments with the standard 5-HT2A receptor radioligand, [3H]ketanserin, with prazosin added to block 1 receptors, a similar Hill slope and Bmax was noted but a two-fold higher KD was found. In competition binding studies using 0.5 nM [3H]MDL 100,907, some 19 standard ligands to various receptors including the 5HT1A, D2, 1, and receptors resulted in estimated KI values that were consistent with [3H]MDL 100,907 selectively binding to the 5-HT2A receptor. A comparison of the KI values for 17 standard 5-HT2A receptor agonists and antagonists displacing [3H]MDL 100,907 versus [3H]ketanserin resulted in a highly significant linear correlation (R2 = 0.96, P<0.001). Taken together these results suggest that [3H]MDL 100,907 is binding to the 5-HT2A receptor with a sub-nanomolar affinity without the use of secondary blocking agents. 相似文献
10.
This paper describes the results of a postmortem study of the effects of tobacco smoking on the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) as well as the binding of [3H]-8-hydroxy-(di-n-propylamino)-tetralin ([3H]-8-OH-DPAT) and [3H]-ketanserin in six discrete regions of human brain. Smoking was associated with significant decreases in the concentrations of 5-HIAA in the hippocampal neocortex (P < 0.001), hippocampal formation (P < 0.05) and the median raphe nuclei (P < 0.05). The 5-HT level of the hippocampal formation was also significantly reduced in smokers (P < 0.05). These changes were accompanied by significant increases in the binding of [3H]-8-OH-DPAT in the hippocampal neocortex (P < 0.01) and hippocampal formation (P < 0.05). [3H]-Ketanserin binding in the brain regions studied was unaffected by smoking. It is concluded that smoking is associated with a regionally selective decrease in the activity of the serotonergic system of the human hippocampus. 相似文献
11.
Stephen J. Peroutka 《Naunyn-Schmiedeberg's archives of pharmacology》1988,338(5):472-475
Summary The specific binding of 3H-quipazine to putative 5-HT3 receptors was analyzed in multiple species. Specific and saturable binding of the radioligand could be detected in both rat (K
D = 1.2 nM; B
max = 3.0 pmol/g) and pig (K
D = 1.3 ± 0.2 nM; B
maX = 1.5 ± 0.2 p/mol/g) cortical membranes. By contrast, no significant specific binding of 3H-quipazine could be detected in human, cow, dog, turtle, mouse, guinea pig, chicken or rabbit brain membranes. These data indicate that marked species variations exist in the presence and/or density of 5-HT3 membrane recognition sites in the central nervous system.
Send offprint requests to Stephen J. Peroutka at the above address 相似文献
12.
Evidence of a functional interaction between serotonin 5-HT1A and 5-HT2 receptor subtypes has been compromised by incomplete experimental designs and conflicting data. To test for such an interaction,
combinations of the 5-HT1A agonist 8-OH-DPAT and the 5-HT2 agonist DOI were administered to rats prior to testing of locomotor activity in the Behavioral Pattern Monitor (BPM). The
BPM is an activity and holeboard chamber that enables analyses of quantitative and qualitative changes in locomotor and investigatory
activity. Dose-response studies of 8-OH-DPAT and DOI alone and in the presence of selected doses of the other drug were performed
in order to allow isobolographic analysis, which characterizes the relationship of two drugs as either additive (no interaction),
supra-additive, or infra-additive. Rats treated with saline, 8-OH-DPAT (6.25, 12.5, 25, or 50 μg/kg SC), DOI (0.15, 0.3, or
0.6 mg/kg SC), or selected combinations of both drugs were tested in the BPM for 1 h. Isobolographic analysis of the effects
on locomotor activity revealed that 8-OH-DPAT and DOI interact in an infra-additive manner. Thus, at a functional level, 5-HT1A and 5-HT2 receptors interact antagonistically in the modulation of locomotor activity.
Received: 15 December 1997 / Final version: 13 February 1998 相似文献
13.
Acute immobilization stress induced by taping four limbs, applying tail pinch stress and electric foot shock stress immediately reduced the frequency of head shakes induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((±)DOI), a 5-HT2A/C agonist in rats. Immobilization stress due to the use of cylinder restraint and forced swimming did not affect 5-HT2A-mediated behavior. Acute immobilization stress did not affect [3H]ketanserin binding to the 5HT2A receptor in the prefrontal cortex and hippocampus. Presynaptic serotonergic lesions with 5,7-dihydroxytryptamine (5,7-DHT) did not affect the reduction in 5-HT2A-mediated behavior after acute immobilization stress. The decreases in head shake frequency after acute immobilization stress by taping were attenuated by pretreatment with diazepam (2.5 mg/kg IP): This attenuation was reversed by pretreatment with flumazenil (10 mg/kg IP). The reduction in (±)DOI- induced 5-HT2A-mediated behavior caused by stress may be related to a change in agonist affinity to the receptor or changes in other neurotransmitter systems or the effect of PI turnover. 相似文献
14.
M. F. Poirier A. M. Galzin C. Pimoule H. Schoemaker K. H. Le Quan Bui P. Meyer C. Gay H. Loo S. Z. Langer 《Psychopharmacology》1988,94(4):521-526
Platelet [3H]-5HT uptake, [3H]-imipramine binding and endogenous 5HT levels were measured in healthy volunteers during short-term (20 days) administration of lithium, and following its withdrawal. The V
max of [3H]-5HT uptake was significantly decreased during lithium treatment. Following lithium withdrawal, platelet [3H]-5HT uptake (V
max) remained decreased and was followed by a pronounced rebound effect in some of the subjects for up to 3 months. The affinity constant (K
m) of [3H-5HT uptake was not modified. Binding of tritiated imipramine during the same period and platelet 5HT levels measured till 14 days after withdrawal was not affected by lithium treatment. As lithium is devoid of in vitro effects on both 5HT uptake and imipramine binding, it is concluded that the effects of lithium on the 5HT transporter do not reflect a direct effect on the transporter complex. Our results indicate that lithium-induced changes at the level of 5HT uptake in platelets are not correlated with concomitant variations in platelet 5HT content and can be dissociated from modifications at the level of imipramine binding sites within the macromolecular complex of the 5HT transporter. Moreover, platelet 5HT uptake is apparently modulated by lithium, with a similar pattern in healthy volunteers and in manic-depressive patients. 相似文献
15.
Rationale: Although there is evidence that central opioid receptors are involved in immunomodulation, it has been only recently that
an endogenous agonist, designated endomorphin-1, possessing high selectivity and affinity for the mu opioid receptor has been
identified. Objective: The present study assesses the immunomodulatory effects of endomorphin-1 in the rat and provides further evaluation of the
antinociceptive effects of endomorphin-1. Methods: Rats were surgically implanted with cannulae directed at the lateral cerebral ventricle. Animals received vehicle or endomorphin-1
at doses of 31.63 or 56.23 μg (ICV) and were tested for antinociception in two different assays, the warm water tail withdrawal
procedure and the hotplate assay. Additional studies assessed the effect of naltrexone on the antinociception produced by
endomorphin-1 in both antinociceptive assessments. Assessments of immune status following endomorphin-1 treatment included
measurements of splenic natural killer cell activity, production of interferon-γ, and lymphocyte proliferative responses to
mitogenic stimulation by Con-A, LPS, and the microbial superantigen, TSST-1. Results: Endomorphin-1 induced significant and naltrexone reversible antinociception 30 and 60 min following drug administration,
as measured by the hotplate assay and warm water tail withdrawal procedure. In marked contrast, endomorphin-1 did not produce
immunomodulatory effects up to 120 min following ICV administration. Conclusions: Endomorphin-1 produces antinociception but does not induce immunomodulatory effects in the rat. These findings suggest that
it is possible to develop therapeutic strategies for separating antinociception and immunomodulatory properties through the
mu opioid receptor.
Electronic Publication 相似文献
16.
Fokko Bosker Dorien Vrinten André Klompmakers H. Westenberg 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(3):347-353
The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin
(TTX), 60 mM K+ and perfusion with Ca2+-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration
of 300 nM of RU 24969, a 5-HT1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic
administration of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of
flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular
5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT1A receptors.
Received: 11 September 1996 / Accepted: 25 November 1996 相似文献
17.
Dirk H. G. Versteeg Tamás Csikós Henk Spierenburg 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(6):595-602
Summary The periaqueductal gray is a brain region of considerable interest. It is innervated by monoamine-containing neurons as well as by a variety of peptidergic fiber systems, and it participates in the regulation of various functions. Virtually nothing is known about monoamine release in the periaqueductal gray and its receptor-mediated modulation. We therefore studied the release of radioactivity from periaqueductal gray slices preloaded with tritriated monoamines, using an in vitro superfusion method.The release of radioactivity from superfused periaqueductal gray slices after preloading of the tissue with [3H]noradrenaline increased upon electrical stimulation in a frequency-dependent manner. The stimulus-evoked release of radioactivity was Ca2+-dependent. Clonidine reduced and yohimbine enhanced the release. The inhibition curve for the effect of clonidine was shifted to the right in the presence of 10–6 M yohimbine. While phenylephrine, isoprenaline, SK&F 38393, quinpirole, carbachol, [Arg8]vasopressin, -MSH and ACTH-(1-24), at a concentration of 10–6 M, did not influence the electrically evoked release of radioactivity, [Leu5]enkephalin reduced it. The selective -opioid receptor agonists [d-Ala2,NMePhe4,Gly-ol5]enkephalin and [d-Arg2,Lys4]-dermorphin-(1–4)-amide reduced the release of radioactivity, whereas the selective opioid receptor agonist [d-Pen2,d-Pen5]enkephalin and the selective K opioid receptor agonist U-69593 had no effect. In the presence of naloxone, which by itself had no effect on the release of radioactivity, the effect of [d-Arg2,Lys4]dermorphin-(1–4)-amide was abolished. These results show that the release of noradrenaline from periaqueductal gray slices is via a Ca2+-dependent. exocytotic process, and that it is modulated through 2-adrenoceptors as well as via -opioid receptors. Though the overflow of radioactivity from slices preloaded with [3H]dopamine in the presence of desipramine was measurable, there are reasons to assume that we are dealing here with the release of tritiated catecholamines from a population of nerve endings consisting of noradrenergic and dopaminergic terminals.The release of radioactivity from periaqueductal gray slices preloaded with [3H]5-hydroxytryptamine upon elevation of the K+ concentration in the superfusion medium was much more pronounced than that induced by electrical stimulation. The K+-evoked release of radioactivity was almost completely abolished in the absence of Cat2+; showing that the release is via a Ca2+-dependent process. 5-Hydrotryptamine reduced the K+-evoked release of radioactivity in a concentration-dependent manner.Some of these data were presented at the XIth International Congress of Pharmacology, 1–6 July 1990, Amsterdam, The Netherlands (Eur J Pharmacol 183:408)
Send offprint requests to D. H. G. Versteeg at the above address 相似文献
18.
A. Segonzac T. Tateishi S. Z. Langer 《Naunyn-Schmiedeberg's archives of pharmacology》1984,328(1):33-37
Summary [3H]-tryptamine is taken up by rabbit platelets through an active and staurable process which is temperture sensitive, sodium-dependent and inhibited by imipramine and non-tricyclic 5-hydroxytryptamine (5-HT) uptake blockers.There is an excellent correlation between the Ki for the inhibition of [3H]-tryptamine and [3H]-5-HT uptake in rabbit platelets for a series of 5-HT uptake blockers. These results indicate that [3H]-tryptamine is actively transported through the membrane of blood platelets by the same carrier that transports 5-HT. 相似文献
19.
3-(3-Hydroxyphenyl)-N-n-propyliperidine (3-PPP) is most effective in inhibiting [3H]apomorphine binding in rat striatal membranes, with Ki values of 63 nM. 3-PPP was six to 27 times less effective when it competed with the binding of [3H]dopamine or [3H]spiperone in calf and rat striatal membranes. At concentrations up to 10 μM, 3-PPP failed to substitute for dopamine in the activation of adenylate cyclase in rat striatal membranes. 3-PPP at 4.8-5 μM caused 50% inhibition of catecholamine uptake in synaptosomes of corpus striatum and hypothalamus, therefore appearing to be a relatively weak uptake inhibitor. The higher affinity of 3-PPP for [3H]apomorphine binding sites is consistent with its binding to a subset of dopamine receptors which are characterized by a high affinity for both the agonist and antagonist of dopamine. 相似文献
20.
A. Zharkovsky A. M. Tötterman J. Moisio L. Ahtee 《Naunyn-Schmiedeberg's archives of pharmacology》1993,347(5):483-486
Summary The effect of chronic administration of dihydropyridine calcium channel antagonist nimodipine (1 mg/kg/day) given concurrently with morphine on the signs of morphine withdrawal and on the [3H]nitren-dipine binding in the rat brain has been investigated. Chronic morphine administration in increasing daily doses from 20 mg/kg to 70 mg/kg for 24 days and consequent withdrawal for 24 h induced loss of body weight, wet dog shakes, episodes of writhing and yawning behaviour. The density of [3H]nitrendipine binding was elevated in the cortex and limbic structures but not in the striatum after chronic morphine treatment. Chronic concurrent administration of nimodipine prevented the loss of body weight and reduced the scores of wet dog shakes and writhing, but did not affect yawning behaviour at 24h after morphine withdrawal. The concurrent nimodipine treatment also prevented the rise in the density of central dihydropyridine binding sites which occurred upon chronic morphine treatment. These results suggest that chronic nimodipine treatment attenuates the development of the withdrawal signs which occur upon the termination of chronic morphine treatment by preventing the up-regulation of the central dihydropyridine-sensitive binding sites.
Correspondence to: L. Ahtee at the above address 相似文献