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1.
We prepared slices from midbrain containing the raphe nuclei and from hippocampus of rats. The brain slices were loaded with [ 3H]serotonin and superfused in order to measure the release of radioactivity at rest and in response to electrical stimulation. No difference was observed in the resting and stimulated fractional release of tritium in the somatodendritic and axon terminal parts of serotonergic neurons. The selective 5-HT 1A receptor agonist 8-OH-DPAT decreased the electrically induced tritium effux from raphe nuclei slices preloaded with [ 3H]serotonin, and this inhibition was reversed by 5-HT 1A receptor antagonist (+)WAY-100135. The 5-HT 1B receptor agonist CGS-12066B but not 8-OH-DPAT, inhibited the stimulation-evoked tritium efflux from hippocampal slices after labeling with [ 3H]serotonin. The electrical stimulation-evoked tritium efflux in raphe nuclei slices incubate with [ 3H]serotonin was completely external Ca 2+-dependent, and omega-conotoxin GVIA and Cd 2+, but not diltiazem, inhibited the tritium overflow. In raphe nuclei slices 4-aminopyridine enhanced the electrical stimulation-induced trititum release in a concentration-dependent manner. The inhibition of tritium efflux by 8-OH-DPAT was abolished with 4-aminopyridine. Glibenclamide or tolbutamide proved to be ineffective. These data indicate that (1) different 5-HT receptor subtypes (5-HT 1A and 5-HT 1B) regulate dendritic and axon terminal 5-HT release; (2) serotonin release from the dendrites may be regulated by the voltage-sensitive N-type Ca 2+ channels; (3) the 5-HT 1A receptor-mediated inhibition of serotonin release may be due to opening of voltage-sensitive K + channels. 相似文献
2.
1. Aim: The role of the serotonin transporter (SERT) is to remove serotonin (5-HT) from the synaptic space. In vitro studies have shown that 5-HT uptake via SERT is influenced by the availability of its substrate, 5-HT. We used RN46A cells, a line that expresses SERT, to investigate 5-HT regulation of 5-HT uptake and the intracellular signaling pathways involved. RN46A cells also express mRNAs for 5-HT receptors (5-HT 1A, 5-HT 1B, 5-HT 2A, and 5-HT 2C) and as cAMP and intracellular Ca 2+ are modulated by different 5-HT receptors, we studied both pathways.2. Methods: 5-HT uptake was determined as imipramine-inhibitable uptake of [ 3H]5-HT, intracellular cAMP was measured by RIA and intracellular Ca 2+ changes were determined using the ratiometric method of intracellular Ca 2+ imaging.3. Results: For uptake experiments, cells were kept for 30 min either with or without 1 μM 5-HT in the medium before measuring uptake. Removal of 5-HT for 30 min significantly decreased [ 3H]5-HT uptake. The absence of 5-HT for 15 min failed to induce any changes in intracellular cAMP levels. Removal of 5-HT from the medium did not change intracellular Ca 2+ levels either; however, adding 1 μM 5-HT after 5 min in 5-HT-free conditions rapidly increased intracellular Ca 2+ levels in 50% of the cells. The remaining cells showed no changes in the intracellular Ca 2+ levels.4. Conclusions: We have shown that in RN46A cells, that endogenously express SERT and mRNAs for several 5-HT receptors, changes in 5-HT levels influence 5-HT uptake rate as well as induce changes in intracellular Ca 2+ levels. This suggests that 5-HT may utilize intracellular Ca 2+ to regulate 5-HT uptake. 相似文献
4.
The effects were studied of short-term (1 week) versus long-term (2-3 weeks) fluoxetine treatment of primary cultures of mouse astrocytes, differentiated by treatment with dibutyryl cyclic AMP. From previous experiments it is known that acute treatment with fluoxetine stimulates glycogenolysis and increases free cytosolic Ca 2+ concentration ([Ca 2+] i]) in these cultures, whereas short-term (one week) treatment with 10 M down-regulates the effects on glycogen and [Ca 2+] i, when fluoxetine administration is renewed (or when serotonin is administered). Moreover, antagonist studies have shown that these responses are evoked by activation of a 5-HT 2 receptor that is different from the 5-HT 2A receptor and therefore at that time tentatively were interpreted as being exerted on 5-HT 2C receptors. In the present study the cultures were found by RT-PCR to express mRNA for 5-HT 2A and 5-HT 2B receptors, but not for the 5-HT 2C receptor, identifying the 5-HT 2 receptor activated by fluoxetine as the 5-HT 2B receptor, the most recently cloned 5-HT 2 receptor and a 5-HT receptor known to be more abundant in human, than in rodent, brain. Both short-term and long-term treatment with fluoxetine increased the specific binding of [ 3H]mesulergine, a ligand for all three 5-HT 2 receptors. Long-term treatment with fluoxetine caused an agonist-induced up-regulation of the glycogenolytic response to renewed administration of fluoxetine, whereas short-term treatment abolished the fluoxetine-induced hydrolysis of glycogen. Thus, during a treatment period similar to that required for fluoxetine's clinical response to occur, 5-HT 2B-mediated effects are initially down-regulated and subsequently up-regulated. 相似文献
5.
The protective effects of sarpogrelate (SG), a 5-HT 2A antagonist, were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Changes in cellular levels of high phosphorous energy, NO and Ca 2+ in the heart together with simultaneous recordings of left ventricular developed pressure (LVDP) were monitored using an nitric oxide (NO) electrode, fluorometry and 31P-NMR. The recovery of LVDP from ischemia by reperfusion was 30.1% in the control, while the treatment with SG (5×10 -7 M) in pre- and post-ischemia hearts produced a gradual increase to 73.1 and 53.6%, respectively. At the final stage of ischemia, the intracellular concentration of Ca 2+ ([Ca 2+i) and release of NO increased with no twitching and remained at a high steady level. The addition of SG increased the transient NO signal (T NO) level at the end of ischemia compared with the control, but [Ca 2+] i during ischemia decreased. Meanwhile, mitochondrial Ca 2+ uptake on acidification or Ca 2+ content changes of the perfusate was suppressed by pre-treatment with SG or the K ATP channel opener diazoxide, but not the K ATP channel blocker 5-HD. The myocardial NO elevated with 5-HT in normal Langendorff hearts was suppressed by the treatment with SG. Therefore, the existence of the 5HT 2A receptor in a Langendorff heart was anticipated. By in vitro EPR, SG was found to directly quench the hydroxy radical. Thus, these findings suggested that the 5-HT 2A receptor induced in ischemia–reperfusion plays an important role in the mitochondrial K ATP channel of hearts in close relation with NO and active oxygen radicals. 相似文献
6.
Background Triptans, 5-HT 1B/ID agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca 2+ channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca 2+ channels are not yet documented. Results In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca 2+ channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba 2+ currents (I Ba) passing through Ca 2+ channels. Zolmitriptan (0.1–100 μM) reduced the size of I Ba in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT 1B/1D antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca 2+ channel blockers inhibited the inhibitory action of zolmitriptan on I Ba, compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT 1B/1D receptor linked to G i/o pathway. Conclusion It is concluded that this zolmitriptan inhibition of HVA Ca 2+ channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan. 相似文献
7.
Abstract: Serotonin 5-HT 2C receptor-mediated intracellular Ca 2+ mobilization was investigated in Chinese hamster ovary (CHO) cells transfected with 5-HT 2C receptors. Fura-2 acetoxymethyl ester was used to investigate the regulation of 5-HT 2C receptor function. CHO cells, transfected with a cDNA clone for the 5-HT 2C receptor, expressed 287 fmol/mg of the receptor protein as determined by mianserin-sensitive [ 3H]mesulergine binding ( KD = 0.49 n M). The addition of 5-HT mobilized intracellular Ca 2+ in a dose-dependent fashion, ranging from a basal level of 99 ± 1.8 up to 379 ± 18 n M, with an EC 50 value for 5-HT of 0.029 µ M. Exposure to 5-HT, 1-(3-chlorophenyl)piperazine dihydrochloride (a 5-HT 2C agonist), and 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (a 5-HT 2C and 5-HT 2A agonist) resulted in increased intracellular Ca 2+ levels. Mianserin, mesulergine, ritanserin, and ketanserin each blocked 5-HT-mediated intracellular Ca 2+ mobilization more effectively than spiperone. The receptor was rapidly desensitized by preexposure to 5-HT in a time- and concentration-dependent manner. Mezerein and phorbol 12-myristate 13-acetate, protein kinase C activators, weakly inhibited the intracellular Ca 2+ mobilization induced by 10 µ M 5-HT. Furthermore, the protein kinase C inhibitor H-7 partially prevented the protein kinase C activator-induced inhibition of the 5-HT-mediated increase in intracellular Ca 2+ concentration. The desensitization induced by pretreatment with 5-HT was blocked by W-7, added in conjunction with 5-HT, and partially inhibited by W-5, a nonselective inhibitor of protein kinases and weak analogue of W-7. Therefore, the 5-HT 2C receptor may be connected with protein kinase C and calcium/calmodulin turnover. These results suggest that 5-HT 2C receptor activation mobilizes Ca 2+ in CHO cells and that the acute desensitization of the receptor may be due to calmodulin kinase-mediated feedback. 相似文献
8.
1. The serotonin type 1A (5-HT 1A) receptors are members of a superfamily of seven transmembrane domain receptors that couple to GTP-binding regulatory proteins (G-proteins). We have studied the modulation of agonist binding to 5-HT 1A receptors from bovine hippocampus by metal ions and guanine nucleotide.2. Bovine hippocampal membranes containing the 5-HT 1A receptor were isolated. These membranes exhibited high-affinity binding sites for the specific agonist [ 3H]OH-DPAT.3. The agonist binding is inhibited by monovalent cations Na +, K +, and Li + in a concentration-dependent manner. Divalent cations such as Ca 2+, Mg 2+, and Mn 2+, on the other hand, show more complex behavior and induce enhancement of agonist binding up to a certain concentration. The effect of the metal ions on agonist binding is strongly modulated in the presence of GTP--S, a nonhydrolyzable analogue of GTP, indicating that these receptors are coupled to G-proteins.4. To gain further insight into the mechanisms of agonist binding to bovine hippocampal 5-HT 1A receptors under these conditions, the binding affinities and binding sites have been analyzed by Scatchard analysis of saturation binding data. Our results are relevant to ongoing analyses of the overall regulation of receptor activity for G-protein-coupled seven transmembrane domain receptors. 相似文献
9.
Abstract: We found in cultured glioma (C6BU-1) cells that excitatory amino acids (EAAs) such as glutamate, N-methyl-d -aspartate (NMDA), aspartate, and metabotropic glutamate receptor agonist trans-(±)-1-amino-1,3-cyclopentanedicarboxylate caused an increase in the inositol 1,4,5-trisphosphate formation and the intracellular Ca 2+ concentration ([Ca 2+] i) in the absence of extracellular Mg 2+ and Ca 2+. Pertussis toxin treatment abolished this glutamate-induced [Ca 2+] i increase. Various antagonists against NMDA receptor-ion channel complex, such as Mg 2+, d -2-amino-5-phosphonovalerate (d -APV), HA-966, and MK-801, also inhibited the increase in [Ca 2+] i induced by glutamate. These results indicate that these metabotropic EAA receptors coupled to pertussis toxin-susceptible GTP-binding protein and phospholipase C system in C6BU-1 glioma cells have the pharmacological properties of NMDA receptor-ion channel complexes. We also found that in the presence of Mg 2+ these metabotropic receptors resemble the NMDA receptor-ion channel complex interacted with 5-hydroxytryptamine 2 (5-HT 2) receptor signaling. EAAs inhibited 5-HT 2 receptor-mediated intracellular Ca 2+ mobilization and inositol 1,4,5-trisphosphate formation in a concentration-dependent manner. The inhibitory effect of glutamate was reversed by various NMDA receptor antagonists (d -APV, MK-801, phencyclidine, and HA-966), but l -APV failed to block the inhibitory effect of glutamate. The same result was observed in the absence of extracellular Ca 2+. In addition, this inhibitory effect on 5-HT 2 receptor-mediated signal transduction was abolished by treatment of C6BU-1 cells with pertussis toxin, whereas 5-HT 2 receptor-mediated [Ca 2+] i increase was not abolished by pertussis toxin treatment. We can, therefore, conclude that the inhibitory effect of glutamate is not a result of the influx of Ca 2+ through the ion channel and that it operates via metabotropic glutamate receptors, having NMDA receptor-ion channel complex-like properties and being coupled with pertussis toxin-sensitive GTP-binding protein and phospholipase C. 相似文献
10.
Abstract: The serotonin 5-HT 3 receptor, a ligand-gated ion channel, has previously been shown to be present on a subpopulation of brain nerve terminals, where, on activation, the 5-HT 3 receptors induce Ca 2+ influx. Whereas postsynaptic 5-HT 3 receptors induce depolarization, being permeant to Na + and K +, the basis of presynaptic 5-HT 3 receptor-induced calcium influx is unknown. Because the small size of isolated brain nerve terminals (synaptosomes) precludes electrophysiological measurements, confocal microscopic imaging has been used to detect calcium influx into them. Application of 100 n M 1-( m-chlorophenyl)biguanide (mCPBG), a highly specific 5-HT 3 receptor agonist, induced increases in internal free Ca 2+ concentration ([Ca 2+] i) and exocytosis in a subset of corpus striatal synaptosomes. mCPBG-induced increases in [Ca 2+] i ranged from 1.3 to 1.6 times over basal values and were inhibited by 10 n M tropisetron, a potent and highly specific 5-HT 3 receptor antagonist, but were insensitive to the removal of external free Na + (substituted with N-methyl-d -glucamine), to prior depolarization induced on addition of 20 m M K +, or to voltage-gated Ca 2+ channel blockade by 10 µ M Co 2+/Cd 2+ or by 1 µ Mω-conotoxin MVIIC/1 µ Mω-conotoxin GVIA/200 n M agatoxin TK. In contrast, the Ca 2+ influx induced by 5-HT 3 receptor activation in NG108-15 cells by 1 µ M mCPBG was substantially reduced by 10 µ M Co 2+/Cd 2+ and was completely blocked by 1 µ M nitrendipine, an L-type Ca 2+ channel blocker. We conclude that in contrast to the perikaryal 5-HT 3 receptors, presynaptic 5-HT 3 receptors appear to be uniquely calcium-permeant. 相似文献
11.
Abstract: Recently, two naturally occurring amino acid substitutions were identified in the C-terminal region of the serotonin 5-HT 2A receptor. One of these, His 452Tyr, has a rarer allele Tyr frequency of 9%. If 452Tyr alters 5-HT 2A function, it would thus be a candidate allele for human neurobehavioral variation. The present study was designed to evaluate the potential influence of the 452His and 452Tyr alleles on cellular 5-HT 2A functions. Platelet 5-HT 2A binding and 5-HT-induced Ca 2+ response were compared in eight 452His/ 452His homozygous and eight 452His/ 452Tyr heterozygous individuals matched for sex, age, and diagnosis (all were patients with seasonal affective disorder). There was no difference in 5-HT 2A binding measured using 125I-lysergic acid diethylamide. Nor were levels of G-protein subunits or PKC α, δ, ε, or ζ significantly altered. However, when Ca 2+ response was stimulated by 2, 5, 10, or 25 µ M 5-HT, significant differences were found. In 452His/ 452Tyr heterozygotes, 452Tyr was associated with both smaller peak amplitude in Ca 2+ mobilization and a different time course of response, with slower peak latency and longer half-time in 452His/ 452Tyr heterozygotes compared with 452His/ 452His homozygotes. The overall difference in the response of the 5-HT 2A receptor in individuals with 452Tyr was a blunting of the shape of the Ca 2+ mobilization peak. The data reported here suggest that the primary sequence of this intracellular domain is important in function of the receptor and that the 452His and 452Tyr 5-HT 2A alleles should be carefully evaluated for effects on human neurobehavioral variation. 相似文献
12.
The presence of serotonin 5-HT 1A receptors and their physiological role were further characterized in the goldfish retina. The effects of the 5-HT 6/7 receptor antagonists pimozide, fluphenazine and amoxapine, the 5-HT 1A receptor antagonist WAY-100,135, and the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, on the 5-HT 1A receptor agonist [ 3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to retinal membranes, were evaluated. In addition, the effects of serotonin, 8-hydroxy-2-(di-n-propylamino)tetralin, WAY-100,135, the adenylate cyclase inhibitors SQ22536 and MDL12330A, and the cyclic AMP analog 8-bromoadenosine-3:5 cyclic monophosphate were also studied on neuritic outgrowth from retinal explants. WAY-100,135 but not 5-HT 6/7receptor antagonists inhibited [ 3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to retinal membranes N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline decreased [ 3H]8-hydroxy-2-(di-n-propylamino)tetralin binding sites up to 70%, while receptor turnover was similar to that reported in other tissues. Serotonin and 8-hydroxy-2-(di-n-propylamino)tetralin stimulated cyclic AMP production, both ex vivo and in vitro, and these increases were related to inhibition of neuritic outgrowth. The inhibitory effect was reduced by SQ22536 and by WAY-100,135, and was mimicked by 8-bromoadenosine-3:5cyclic monophosphate. This study supports previous findings about the role of serotonin as a regulator of axonal outgrowth during in vitro regeneration of the goldfish retina and demonstrates that this effect is mediated, at least in part, by 5-HT 1A receptors through a mechanism which involves an increase of cyclic AMP levels. 相似文献
13.
[ 3H]Spiroxatrine was examined as a potential ligand for the labeling of 5-HT 1A sites in the rat hippocampus. Analysis of the binding of [ 3H]spiroxatrine in the absence and presence of varying concentrations of three monoamine neurotransmitters revealed that serotonin (5-HT) had high affinity (IC 50= 20.7 nM for the [ 3H]spiroxatrine binding sites, consistent with the labeling of 5-HT 1 sites, while dopamine and norepinephrine had very low affinity (IC 50=57600 nM and >10 −4 M respectively). Saturation studies of the binding of [ 3H]spiroxatrine revealed a single population of sites with a K d=2.21 nM. Further pharmacologic characterization with the 5-HT 1A ligands 8-hydroxy-2-(di-n-propylamino) tetralin, ipsapirone, and WB4101 and the butyrophenone compounds spiperone and haloperidol gave results that were consistent with [ 3H]spiroxatrine labeling 5-HT 1A sites. This ligand produced stable, reproducible binding with a good ratio of specific to nonspecific binding. The binding of [ 3H]spiroxatrine was sensitive to GTP, suggesting that this ligand may act as an agonist. This was supported by the finding that spiroxatrine inhibits forskolin-stimulated adenylate cyclase activity (a proposed 5-HT 1A receptor model) in the rat hippocampus. Since [ 3H]spiroxatrine is structurally distinct from other currently available radioligands for the 5-HT 1A site, it should provide new information about the properties of this putative serotonergic receptor. 相似文献
14.
Abstract: Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine 2A (5-HT 2A) or 5-HT 2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT 2C receptor (pEC 50 = 7.80 ± 0.06) compared with the 5-HT 2A receptor (pEC 50 = 7.30 ± 0.08). Activation of the 5-HT 2A receptor caused a transient fourfold increase in intracellular Ca 2+ concentration. Whole-cell recordings of cells clamped at ?50 mV demonstrated a small inward current (2 pA) in response to 10 µ M 5-HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [ d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI), 5-methoxy- N,N-dimethyltryptamine, and mescaline] and three nonhallucinogenic drugs ( m-chlorophenylpiperazine, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5-HT revealed selective activation of the 5-HT 2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5-methoxy- N,N-dimethyltryptamine were relatively nonselective, whereas m-chlorophenylpiperazine selectively activated the 5-HT 2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT 2C receptor, whereas activity at the 5-HT 2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action. 相似文献
15.
Caffeine, a stimulant largely consumed around the world, is a non-selective adenosine receptor antagonist, and therefore caffeine actions at synapses usually, but not always, mirror those of adenosine. Importantly, different adenosine receptors with opposing regulatory actions co-exist at synapses. Through both inhibitory and excitatory high-affinity receptors (A1R and A2R, respectively), adenosine affects NMDA receptor (NMDAR) function at the hippocampus, but surprisingly, there is a lack of knowledge on the effects of caffeine upon this ionotropic glutamatergic receptor deeply involved in both positive (plasticity) and negative (excitotoxicity) synaptic actions. We thus aimed to elucidate the effects of caffeine upon NMDAR-mediated excitatory post-synaptic currents (NMDAR-EPSCs), and its implications upon neuronal Ca2+ homeostasis. We found that caffeine (30–200 μM) facilitates NMDAR-EPSCs on pyramidal CA1 neurons from Balbc/ByJ male mice, an action mimicked, as well as occluded, by 1,3-dipropyl-cyclopentylxantine (DPCPX, 50 nM), thus likely mediated by blockade of inhibitory A1Rs. This action of caffeine cannot be attributed to a pre-synaptic facilitation of transmission because caffeine even increased paired-pulse facilitation of NMDA-EPSCs, indicative of an inhibition of neurotransmitter release. Adenosine A2ARs are involved in this likely pre-synaptic action since the effect of caffeine was mimicked by the A2AR antagonist, SCH58261 (50 nM). Furthermore, caffeine increased the frequency of Ca2+ transients in neuronal cell culture, an action mimicked by the A1R antagonist, DPCPX, and prevented by NMDAR blockade with AP5 (50 μM). Altogether, these results show for the first time an influence of caffeine on NMDA receptor activity at the hippocampus, with impact in neuronal Ca2+ homeostasis. 相似文献
16.
Low levels of docosahexaenoic acid (DHA) have been linked to a number of mental illnesses such as memory loss, depression and schizophrenia. While supplementation of DHA is beneficial in improving memory and cognition, the influence of dietary fats on the neurotransmitters and receptors involved in cognitive function is still not known. The aim of this study was to investigate serotonin receptor (5-HT 1A and 5-HT 2A), cannabinoid receptor (CB1) and gamma-aminobutyric acid type A (GABA A) receptor binding densities in the brain of male rats fed a high-saturated-fat (HF) diet, as well as the effect of DHA supplementation on HF diet. Alterations of these receptors in the post-mortem rat brain were detected by [ 3H]-WAY-100635, [ 3H]-ketanserin, [ 3H]-CP-55,940 and [ 3H]-muscimol binding autoradiography, respectively. In the hippocampus, the 5-HT 1A, CB1 and GABA A receptor binding densities significantly increased in response to an HF diet, while in the hypothalamus, 5-HT 1A and CB1 binding densities significantly increased in HF-fed rats. Importantly, DHA supplementation prevented the HF-induced increase of receptors binding density in the hippocampus and hypothalamus. Furthermore, DHA supplementation attenuated 5-HT 2A receptor binding density in the caudate putamen, anterior cingulate cortex and medial mammillary nucleus, which was also increased in HF group. This study showed that an HF diet increased 5-HT 1A, 5-HT 2A, CB1 and GABA A receptor binding densities in the brain regions involved in cognitive function and that dietary DHA can attenuate such alterations. These findings provide insight into the mechanism by which DHA supplementation ameliorates reduced cognitive function associated with an HF diet. 相似文献
17.
Characteristics for the up-regulated response in the concentration of intracellular calcium ion ([Ca 2+]
i
) and in the sodium ion (Na +) current by serotonin (5-HT) were investigated in differentiated neuroblastoma × glioma hybrid NG108-15 (NG) cells. The results
for the changes in [Ca 2+]
i
by 5-HT were as follows, (1) The 5-HT-induced Ca 2+ response was inhibited by 3 × 10 −9 M tropisetron (a 5-HT 3 receptor blocker), but not by other types of 5-HT receptor blockers; (2) The 5-HT-induced Ca 2+ response was mainly inhibited by calciseptine (a L-type Ca 2+ blocker), but not by other types of Ca 2+ channel blockers or 10 −7 M TTX (a voltage-sensitive Na + channel blocker); (3) When the extracellular Na + was removed by exchange with choline chloride or N-methyl- d-glucamine, the 5-HT-induced Ca 2+ response was extremely inhibited. The results for the 5-HT-induced Na + current by the whole cell patch-clamp technique were as follows, (1) The 5-HT-induced Na + current in differentiated cells was significantly larger than that in undifferentiated cells; (2) The ED 50 value for 5-HT-induced Na + current in undifferentiated and differentiated cells was almost the same, about 4 × 10 −6 M each other; (3) The 5-HT-induced Na + current was completely blocked by 3 × 10 −9 M tropisetron, but not by other 5-HT receptor antagonists and 10 −7 M TTX. These results suggested that 5-HT-induced Ca 2+ response in differentiated NG cells was mainly due to L-type voltage-gated Ca 2+ channels allowing extracellular Na + to enter via 5-HT 3 receptors, but not through voltage-gated Na + channels. 相似文献
18.
It has been shown that anti-cancer drug induces secretion of serotonin (5-HT) from small intestine which activates serotonin type 3 (5-HT 3) receptor to cause nausea and vomiting. In general, antagonist for 5-HT 3 receptor is used as anti-emetics during chemotherapy. However, we found that anti-cancer drug irinotecan itself inhibits 5-HT-gated current through the homomeric 5-HT 3A and heteromeric 5-HT 3AB receptor in a concentration-dependent manner. The inhibitory effect of irinotecan on 5-HT 3A receptor was more potent than that on 5-HT 3AB receptor. On the other hand, SN-38, a metabolite of irinotecan, had no effect on the responsiveness. Our findings suggest that irinotecan itself could have anti-emetic activities through inhibition of the 5-HT 3A and 5-HT 3AB receptor. 相似文献
20.
Thy-1 glycoprotein is expressed in rat glomerular mesangial cells, and anti-Thy-1 nephritis induced by anti-Thy-1 antibodies is a model of human renal diseases. In this study, we examined Thy-1-mediated biological reactions in cultured rat glomerular mesangial cells utilizing two anti-Thy-1 monoclonal antibodies (mAbs), 1-22-3 and OX-7. Incubation of the cells with these mAbs resulted in increased inositol trisphosphate (IP 3) levels. The rise in IP 3 produced by mAb 1-22-3 was greater than that produced by mAb OX-7 at the same dose. Incubation of mesangial cells with these mAbs resulted in an increase in the intracellular free calcium concentration ([Ca 2+]i). mAb 1-22-3 induced a sustained increase in [Ca 2+]i, while that induced by mAb OX-7 lasted 1-2 min, then decreased to the basal level. An transient increase in [Ca 2+]i was also observed in Ca 2+-free medium, indicating that these [Ca 2+]i increases are due to release of Ca 2+ from internal stores by IP 3 without calcium flux across cell membrane. When cells were pretreated with protein tyrosine kinase (PTK) inhibitors (herbimycin A or genistein), Thy-1-mediated increases in [Ca 2+]i were inhibited. These data suggest that Thy-1 induces the production of IP 3 (including inositol 1,4,5-triphosphate, an intracellular Ca 2+-releasing factor) and that PTKs may contribute to the Thy-1-mediated elevation of [Ca 2+]i which presumably results from phospholipase C activation following Thy-1-mediated signaling in rat mesangial cells. © 1996 Wiley-Liss, Inc. 相似文献
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