共查询到20条相似文献,搜索用时 46 毫秒
1.
June C. Serravezza Frances B. Wheeler Robert L. DeHaan Louis J. Elsas 《Developmental biology》1981,84(2):417-424
We have compared insulin binding by heart cells at 7 and 14 days of development. Species specificity, optimum pH, temperature relationships, and time to equilibrium for binding of insulin were the same in both 7 and 14-day systems. Curvilinear Scatchard plots for chicken insulin binding were demonstrated. Binding affinities and capacities were calculated based on a two-receptor model including a specific high-affinity receptor and a less specific low-affinity receptor that bound insulin and other growth peptides. Apparent association constants (KA) were 4.0 and 0.05 nM?1 and binding capacities were 600 and 9000 sites per cell for high- and low affinity receptors, respectively. We have also investigated the ability of insulin to regulate binding to its own receptors. Chick heart cells from 7- and 14-day embryos, cultured for 44 hr in insulin-enriched medium (3.4 μM), bound 50% less insulin (down-regulated) than control cells. At both developmental stages, down regulation was primarily a reduction in binding to the high-affinity receptor. The low-affinity receptor was less susceptible to down regulation and retained its ability to mediate maximal insulin stimulation of amino acid transport. 相似文献
2.
2- and 8-alkynyl-9-ethyladenines: Synthesis and biological activity at human and rat adenosine receptors 总被引:1,自引:1,他引:0
Volpini R Costanzi S Lambertucci C Vittori S Martini C Trincavelli ML Klotz KN Cristalli G 《Purinergic signalling》2005,1(2):173-181
The synthesis of a series of 9-ethyladenine derivatives bearing alkynyl chains in 2- or 8-position was undertaken, based on the observation that replacement of the sugar moiety in adenosine derivatives with alkyl groups led to adenosine receptor antagonists. All the synthesized compounds were tested for their affinity at human and rat A1, A2A, and A3 adenosine receptors in binding assays; the activity at the human A2B receptor was determined in adenylyl cyclase experiments. Biological data showed that the 2-alkynyl derivatives possess good affinity and are slightly selective for the human A2A receptor. The same compounds tested on the rat A1 and A2A subtypes showed in general lower affinity for both receptors. On the other hand, the affinity of the 8-alkynyl derivatives at the human A1, A2A, and A2B receptors proved to be lower than that of the corresponding 2-alkynyl derivatives. On the contrary, the affinity of the same compounds for the human A3 receptor was improved, resulting in A3 selectivity. As in the case of the 2-alkynyl-substituted compounds, the 8-alkynyl derivatives showed decreased affinity for rat receptors. However, it is worthwhile to note that the 8-phenylethynyl-9-ethyladenine was the most active compound of the two series (Ki in the nanomolar range) at both the human and rat A3 subtype. Docking experiments of the 2- and 8-phenylethynyl-9-ethyladenines, at a rhodopsin-based homology model, gave a rational explanation of the preference of the human A3 receptor for the 8-substituted compound. 相似文献
3.
María Isabel Nieto María Carmen Balo José Brea Olga Caamaño María Isabel Cadavid Franco Fernández Xerardo García Mera Carmen López José Enrique Rodríguez-Borges 《Bioorganic & medicinal chemistry》2009,17(9):3426-3432
In order to identify a high-affinity, selective antagonist for the A2B subtype adenosine receptor, more than 40 1,8-disubstituted-3-(3-methoxypropyl) xanthines were prepared and evaluated for their binding affinity at recombinant human adenosine receptors, mainly of the A2A and A2B subtypes. Some of the 1-ethyl-3-(3-methoxypropyl)-8-aryl substituted derivatives 15(a–m) showed moderate-to-high affinity at human A2B receptors, with compound 15d showing A2B selectivity over the other A receptors assayed (A1, A2A, A3) of 34-fold or over. 相似文献
4.
Marcel Lindemann Sonja Hinz Winnie Deuther-Conrad Vigneshwaran Namasivayam Sladjana Dukic-Stefanovic Rodrigo Teodoro Magali Toussaint Mathias Kranz Cathleen Juhl Jörg Steinbach Peter Brust Christa E. Müller Barbara Wenzel 《Bioorganic & medicinal chemistry》2018,26(16):4650-4663
On the basis of a pyrazine core structure, three new adenosine A2B receptor ligands (7a–c) were synthesized containing a 2-fluoropyridine moiety suitable for 18F-labeling. Compound 7a was docked into a homology model of the A2B receptor based on X-ray structures of the related A2A receptor, and its interactions with the adenosine binding site were rationalized. Binding affinity data were determined at the four human adenosine receptor subtypes. Despite a rather low selectivity regarding the A1 receptor, 7a was radiolabeled as the most suitable candidate (Ki(A2B)?=?4.24?nM) in order to perform in vivo studies in mice with the aim to estimate fundamental pharmacokinetic characteristics of the compound class. Organ distribution studies and a single PET study demonstrated brain uptake of [18F]7a with a standardized uptake value (SUV) of ≈1 at 5?min post injection followed by a fast wash out. Metabolism studies of [18F]7a in mice revealed the formation of a blood–brain barrier penetrable radiometabolite, which could be structurally identified. The results of this study provide an important basis for the design of new derivatives with improved binding properties and metabolic stability in vivo. 相似文献
5.
Bertarelli DC Diekmann M Hayallah AM Rüsing D Iqbal J Preiss B Verspohl EJ Müller CE 《Purinergic signalling》2006,2(3):559-571
Adenosine A2B receptors of native human and rodent cell lines were investigated using [3H]PSB-298 [(8-{4-[2-(2-hydroxyethylamino)-2-oxoethoxy]phenyl}-1-propylxanthine] in radioligand binding studies. [3H]PSB-298 showed saturable and reversible binding. It exhibited a KD value of 60 ± 1 nM and limited capacity (Bmax = 3.511 fmol per milligram protein) at recombinant human adenosine A2B receptors expressed in human embryonic kidney cells (HEK-293). The addition of sodium chloride (100 mM) led to a threefold increase in the number of binding sites recognized by the radioligand. The curve of the agonist 5′-N-ethylcarboxamidoadenosine (NECA) was shifted to the right in the presence of NaCl, while the curve of the antagonist PSB-298 was shifted to the left, indicating that PSB-298 may be an inverse agonist at A2B receptors. Adenosine A2B receptors were shown to be the major adenosine A2 receptor subtype on the mouse neuroblastoma x rat glioma hybrid cell line NG108-15 cells. Binding studies at rat INS-1 cells (insulin secreting cell line) demonstrated that [3H]PSB-298 is a selective radioligand for adenosine A2B binding sites in this cell line. 相似文献
6.
《Journal of receptor and signal transduction research》2013,33(3-4):267-280
AbstractThe development of the GABAA/Benzodiazepine receptor (GABAAR) in the red nucleus was studied using 3H-flunitrazepam (FNZ) as the probe. Saturation binding assay showed that the Bmax of the ligand to the membranes of the nucleus increased from 0.50 ± 0.04 nmol/mg protein at postnatal day 4, to 0.71 ± 0.1 and 0.78 ± 0.08 at day 7 and day 10. At day 20 the Bmax decreased to a level near day 4 and persisted until day 40. However, the affinity of 3H-FNZ to the receptor remained quite constant. At least 4 proteins of 51kD, 53kD, 59kD and 62kD in the nucleus were labeled by 3H-FNZ, as revealed from photoaffinity binding and SDS-PAGE. The labeling of 53kD, 59kD and 62kD was high at earlier ages than day 10, whereas the 51kD was predominent from day 10 to day 40. Receptor binding autoradiography of the nucleus also showed that the most dense labeling was seen around day 10. The early transient increase in the GABAAR of the red nucleus may indicate the plasticity of the nucleus in response to environmental changes after birth. 相似文献
7.
Marazziti Donatella Rossi Alessandra Palego Lionella Giannaccini Gino Naccarato Antonio Lucacchini Antonio Cassano Giovanni B. 《Neurochemical research》1997,22(6):753-757
This study aimed at comparing the binding characteristics of [3H]ketanserin, a high-affinity serotonin 2A (5-HT2A) receptor antagonist, in the prefrontal cortex, hippocampus and striatum of human brain post-mortem. The results indicated the presence of a single population of binding sites in all the regions investigated, with no statistical difference in maximum binding capacity (Bmax) or dissociation constant (Kd) values. The pharmacological profile of [3H]ketanserin binding was consistent with the labeling of the 5-HT2A receptor, since it revealed a competing drug potency ranking of ketanserin = spiperone > clozapine = haloperidol > methysergide > mesulergine > 5-HT. In conclusion, the 5-HT2A receptor, as labeled by [3H]ketanserin, would seem to consist of a homogenous population of binding sites and to be equally distributed in human prefronto-cortical, limbic and extrapyramidal structures. 相似文献
8.
Quinone and inhibitor binding to Rhodopseudomonas sphaeroides (R-26 and GA) reaction centers were studied using spectroscopic methods and by direct adsorption of reaction centers onto anion exchange filters in the presence of 14C-labelled quinone or inhibitor. These measurements show that as secondary acceptor, QB, ubiquinone (UQ) is tightly bound in the semiquinone form and loosely bound in the quinone and quinol forms. The quinol is probably more loosely bound than the quinone. o-Phenanthroline and terbutryn, a triazine inhibitor, compete with UQ and with each other for binding to the reaction center. Inhibition by o-phenanthroline of electron transfer from the primary to the secondary quinone acceptor (QA to QB) occurs via displacement of UQ from the QB binding site. Displacement of UQ by terbutryn is apparently accessory to the inhibition of electron transfer. Terbutryn binding is lowered by reduction of QB to Q?B but is practically unaffected by reduction of QA to Q?A in the absence of QB. UQ-9 and UQ-10 have a 5- to 6-fold higher binding affinity to the QB site than does UQ-1, indicating that the long isoprenoid chain facilitates the binding to the QB site. 相似文献
9.
José Enrique Rodríguez-Borges Xerardo García-Mera María Carmen Balo José Brea Olga Caamaño Franco Fernández Carmen López María Isabel Loza María Isabel Nieto 《Bioorganic & medicinal chemistry》2010,18(5):2001-2009
A number of novel xanthines bearing a variety of substituents at positions 1, 3, 7 and 8 were prepared and evaluated for their binding affinity to the human adenosine receptor A1, A2A, A2B and A3 subtypes. Several of the 1,3,8- and 1,3,7,8-substituted xanthines showed moderate-to-high affinity at human A2B and A1 receptors, with the most active compound (14q) having a pKi of 7.57 nM for hA2B receptors and a selectivity over hA2A receptors of 8.1-fold and hA1 receptors of 3.7-fold. 相似文献
10.
《Neurochemistry international》1988,12(2):125-129
GABA receptor binding to mammalian neuronal membranes has been classified into at least 2 subtypes—GABAA and GABAB binding sites. In catfish brain GABAA receptor sites have previously been demonstrated. Evidence is now presented that under appropriate conditions which rule out GABAA receptor binding, [3H]GABA binds to membranes prepared from catfish brain. This binding is bicuculline-insensitive but differs enough from mammalian GABAB binding to cast some doubt on the idea that GABAB receptors exist in catfish brain. Specific binding was detected that was saturable and exhibited a dissociation constant of 4μM. (±)Baclofen, a potent inhibitor in rat brain, was a weak inhibitor, producing a maximum of 43% inhibition. This inhibitory effect could be enhanced, however, in the presence of 320 μM isoguvacine. [3H]GABA binding was unaffected by bicuculline. Thus bicuculline-insensitive GABA binding sites exist in catfish brain but they differ in a number of ways from the GABAB receptor site found in mammals. Furthermore, a third [3H]GABA binding site appears to exist that is both baclofen- and bicuculline-insensitive, yet is inhibited by high concentrations of isoguvacine, a known GABAA agonist. 相似文献
11.
Oligomeric states of the insulin receptor: binding and autophosphorylation properties 总被引:2,自引:0,他引:2
Properties of oligomeric states of the insulin receptor were analyzed by polyacrylamide gel electrophoresis in nondenaturing buffer conditions (ND-PAGE). Partially purified insulin receptors resolve in ND-PAGE as three distinct species: (i) the fast electrophoretic mobility, low molecular mass form manifests intense labeling by iodinated insulin and shows basal and insulin-stimulated autophosphorylation; (ii) the middle, intermediate mobility form exhibits strong labeling by iodinated ligand but does not possess the capacity to be autophosphorylated; (iii) the slow mobility, highest molecular mass form necessitates covalent binding with iodinated hormone to withstand electrophoresis and shows autophosphorylation enhanced by insulin. This receptor form is more heavily labeled by phosphorylation than the low form. At 22 degrees C, binding and autophosphorylation do not appear to be time dependent. At 37 degrees C, binding and autophosphorylation of low and high species attain a maximum after 15 min and then decrease as time of incubation with insulin is prolonged to 120 min; the middle species exhibits a much slower association rate, and its labeling by iodinated hormone becomes more intense with time. Our data show that in cell-free systems insulin receptors appear in various oligomeric states and that the highest molecular mass oligomer exhibits the most pronounced autophosphorylation. This is compatible with the concept that insulin receptor oligomerization provides a mechanism for transmembrane signaling. 相似文献
12.
Flavia Varano Daniela Catarzi Matteo Falsini Diego Dal Ben Michela Buccioni Gabriella Marucci Rosaria Volpini Vittoria Colotta 《Bioorganic & medicinal chemistry letters》2019,29(4):563-569
This paper describes the synthesis of novel 7-amino-thiazolo[5,4-d]pyrimidines bearing different substituents at positions 2, 5 and 7 of the thiazolopyrimidine scaffold. The synthesized compounds 2–27 were evaluated in radioligand binding (A1, A2A and A3) and adenylyl cyclase activity (A2B and A2A) assays, in order to evaluate their affinity and potency at human adenosine receptor subtypes. The current study allowed us to support that affinity and selectivity of 7-amino-thiazolo[5,4-d]pyrimidine derivatives towards the adenosine receptor subtypes can be modulated by the nature of the groups attached at positions 2, 5 and 7 of the bicyclic scaffold. To rationalize the hypothetical binding mode of the newly synthesized compounds, we also performed docking calculations in human A2A, A1 and A3 structures. 相似文献
13.
Lambertucci C Cristalli G Dal Ben D Kachare DD Bolcato C Klotz KN Spalluto G Volpini R 《Purinergic signalling》2007,3(4):339-346
A new series of 2,6,9-trisubstituted adenines (5–14) have been prepared and evaluated in radioligand binding studies for their affinity at the human A1, A2A and A3 adenosine receptors and in adenylyl cyclase experiments for their potency at the human A2B subtype. From this preliminary study the conclusion can be drawn that introduction of bulky chains at the N
6 position of 9-propyladenine significantly increased binding affinity at the human A1 and A3 adenosine receptors, while the presence of a chlorine atom at the 2 position resulted in a not univocal effect, depending
on the receptor subtype and/or on the substituent present in the N
6 position. However, in all cases, the presence in the 2 position of a chlorine atom favoured the interaction with the A2A subtype. These results demonstrated that, although the synthesized compounds were found to be quite inactive at the human
A2B subtype, adenine is a useful template for further development of simplified adenosine receptor antagonists with distinct
receptor selectivity profiles. 相似文献
14.
Monika Sakowicz‐Burkiewicz Katarzyna Kocbuch Marzena Grden Andrzej Szutowicz Tadeusz Pawelczyk 《Journal of cellular biochemistry》2010,109(2):396-405
Development of diabetes is associated with altered expression of adenosine receptors (ARs). Some of these alterations might be attributed to changes in insulin concentration. This study was undertaken to investigate the possible insulin effect on ARs level, and to determine the signaling pathway utilized by insulin to regulate the expression of ARs in rat B lymphocytes. Western blot analysis of B lymphocytes protein extracts indicated that all four ARs were present at detectable levels in the cells cultured for 24 h without insulin (≤10?11 M), although the protein band of A2A‐AR was barely visible. Inclusion of insulin (10?8 M) in the culture medium resulted in an increase of A1‐AR and A2A‐AR protein levels and a significant decrease of A2B‐AR protein, whereas the protein level of A3‐AR remained unchanged. Alterations in the ARs protein content were accompanied by changes in the ARs mRNA levels. Increase of the insulin concentration from 10?11 to 10?8 M resulted in 50% decrease of A2B‐AR mRNA level and two‐, and threefold increase of A1‐AR and A2A‐AR mRNA levels, respectively. Pretreatment of B cells with cycloheximide completely blocked the insulin action on A1‐AR and A2A‐AR mRNA, but not on A2B‐AR expression. Detailed pharmacological analysis demonstrated that insulin‐induced A1‐AR and A2A‐AR mRNA expression through the Ras/Raf‐1/MEK/ERK pathway. The insulin effect on A2B‐AR expression was blocked by p38 MAP kinase inhibitor (SB 203580). Concluding, elevated insulin concentration differentially affects the expression of ARs in B lymphocytes in a fashion that might enhance the various immunomodulatory effects of adenosine. J. Cell. Biochem. 109: 396–405, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
15.
Pretty Mary Abraham Korah P Kuruvilla Jobin Mathew Anitha Malat Shilpa Joy CS Paulose 《Journal of biomedical science》2010,17(1):78
Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find
the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed
a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters Bmax and Kd showed a significant decrease (p < 0.001) whereas 5-HT2A receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin
through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by
combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal
serotonergic function. This has clinical significance in the management of diabetes. 相似文献
16.
María Carmen Balo Jos Brea Olga Caamao Franco Fernndez Xerardo García-Mera Carmen Lpez María Isabel Loza María Isabel Nieto Jos Enrique Rodríguez-Borges 《Bioorganic & medicinal chemistry》2009,17(18):6755-6760
The synthesis of an important set of 3-furfurylxanthine derivatives is described. Binding affinities were determined for rat A1 and human A2A, A2B and A3 receptors. Several of the 3-furfuryl-7-methylxanthine derivatives showed moderate-to-high affinity at human A2B receptors, the most active compound (10d) having a Ki of 7.4 nM for hA2B receptors, with selectivities over rA1 and hA2A receptors up to 14-fold and 11-fold, respectively. Affinities for hA3 receptors were very low for all members of the set. 相似文献
17.
Harada N Himeno A Shigematsu K Sumikawa K Niwa M 《Cellular and molecular neurobiology》2002,22(2):207-226
1. Interaction in the recognition of endothelin-1 (ET-1), a typical bivalent ET receptor-ligand, between ETA and ETB receptors was investigated in the rat anterior pituitary gland, using our quantitative receptor autoradiographic method with tissue sections preserving the cell-membrane structure and ET receptor-related compounds.2. In saturation binding studies with increasing concentrations (0.77–200 pM) of 125I-ET-1 (nonselective bivalent radioligand), 125I-ET-1 binding to the rat anterior pituitary gland was saturable and single with a K
D of 71 pM and a B
max of 120 fmol mg–1. When 1.0 M BQ-123 (ETA antagonist) was added to the incubation buffer, binding parameters were 8.3 pM of K
D and 8.0 fmol mg–1 of B
max, whereas 10 nM sarafotoxin S6c (ETB agonist) exerted little change in these binding parameters (K
D, 72 pM; B
max, 110 fmol mg–1).3. Competition binding studies with a fixed amount (3.8 pM) of 125I-ET-1 revealed that when 1.0 M BQ-123 was present in the incubation buffer, ETB receptor-related compounds such as sarafotoxin S6c, ET-3, IRL1620 (ETB agonist), and BQ-788 (ETB antagonist) competitively inhibited 125I-ET-1 binding with K
is of 140, 18, 350 pM, and 14 nM, respectively, however, these compounds were not significant competitors for 125I-ET-1 binding in the case of absence of BQ-123.4. In cold-ligand saturation studies with a fixed amount (390 pM) of 125I-IRL 1620 (ETB radioligand), IRL1620 bound to a single population of the ETB receptor, and no change was observed in binding characteristics in the presence of 1.0 M BQ-123. 125I-IRL1620 binding was competitively inhibited by ET-1 and ET-3 in the absence of BQ-123, with K
is of 20 and 29 pM, respectively, the affinities being much the same as those of 29 nM, in the presence of 1.0 M BQ-123.5. Two nonbivalent ETA antagonists, BQ-123 and PD151242, were highly sensitive and full competitors for 125I-ET-1 binding (5.0 pM), in the presence of 10 nM sarafotoxin S6c.6. Taken together with the present finding that mRNAs encoding the rat ETA and the ETB receptors are expressed in the anterior pituitary gland, we tentatively conclude that although there are ETA and ETB receptors with a functional binding capability for ET receptor-ligands, the ETB receptor does not independently recognize ET-1 without the aid of the ETA receptor. If this thesis is tenable, then ET-1 can bridge between the two receptors to form an ETA–ETB receptor heterodimer. 相似文献
18.
Dal Ben D Lambertucci C Taffi S Vittori S Volpini R Cristalli G Klotz KN 《Purinergic signalling》2006,2(4):589-594
A series of 2-phenylethynyladenosine (PEAdo) derivatives substituted in the N6- and 4′-position was synthesised and the new derivatives were tested at the four human adenosine receptors stably transfected into Chinese hamster ovary (CHO) cells, using radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assay (A2B). Binding studies showed that the presence of a phenyl ethynyl group in the 2 position of adenosine favoured the interaction with A3 receptors, resulting in compounds endowed with high affinity and selectivity for the A3 subtype. Additional substitution of the N6- and 4′-position increases both A3 affinity and selectivity. The results showed that the new compounds have a good affinity for the A3 receptor and in particular, the N6-methoxy-2-phenylethynyl-5′-N-methylcarboxamidoadenosine, with a Ki at A3 of 1.9 nM and a selectivity A1/A3 and A2A/A3 of 4,800- and 8,600-fold, respectively. Therefore, it is one of the most potent and selective agonists at the human A3 adenosine receptor subtype reported so far. Furthermore, functional assays of inhibition of 10 μM forskolin-stimulated cAMP production via the adenosine A3 receptor revealed that the new trisubstituted adenosine derivatives behave as full agonist of this receptor subtype. Docking analysis of these compounds was performed at a homology model of the human A3 receptor based on the bovine rhodopsin crystal structure as template, and the results are in accordance with the biological data.An erratum to this article can be found at 相似文献
19.
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-HT1A 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-HT1A receptor antagonist (+)WAY-100135. The 5-HT1B 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 Ca2+-dependent, and omega-conotoxin GVIA and Cd2+, 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-HT1A and 5-HT1B) regulate dendritic and axon terminal 5-HT release; (2) serotonin release from the dendrites may be regulated by the voltage-sensitive N-type Ca2+ channels; (3) the 5-HT1A receptor-mediated inhibition of serotonin release may be due to opening of voltage-sensitive K+ channels. 相似文献
20.
5-Hydroxytryptamine2A (5-HT2A) receptor kinetics was studied in cerebral cortex and brain stem of streptozotocin (STZ) induced diabetic rats. Scatchard analysis with [3H] (±) 2,3dimethoxyphenyl-1-[2-(4-piperidine)-methanol] ([3H]MDL100907) in cerebral cortex showed no significant change in maximal binding (Bmax) in diabetic rats compared to controls. Dissociation constant (Kd) of diabetic rats showed a significant decrease (p < 0.05) in cerebral cortex, which was reversed to normal by insulin treatment. Competition studies of [3H]MDL100907 binding in cerebral cortex with ketanserin showed the appearance of an additional low affinity site for 5-HT2A receptors in diabetic state, which was reversed to control pattern by insulin treatment. In brain stem, scatchard analysis showed a significant increase (p < 0.05) in Bmax accompanied by a significant increase (p < 0.05) in Kd. Competition analysis in brain stem also showed a shift in affinity towards a low affinity State for 5-HT2A receptors. All these parameters were reversed to control level by insulin treatment. These results show that in cerebral cortex there is an increase in affinity of 5-HT2A receptors without any change in its number and in the case of brain stem there is an increase in number of 5HT2A receptors accompanied by a decrease in its affinity during diabetes. Thus, from the results we suggest that the increase in affinity of 5-HT2A receptors in cerebral cortex and upregulation of 5-HT2A receptors in brain stem may lead to altered neuronal function in diabetes. 相似文献