共查询到20条相似文献,搜索用时 31 毫秒
1.
Ian P. Holmes Fabrizio Micheli Simon Gaines Olivier Lorthioir Steve P. Watson Romano Di Fabio Gabriella Gentile Christian Heidbreder Chiara Savoia Angela Worby 《Bioorganic & medicinal chemistry letters》2009,19(16):4799-4801
The synthesis and SAR of a new series of potent and selective dopamine D3 receptor antagonists is reported. 相似文献
2.
Ortega R Hübner H Gmeiner P Masaguer CF 《Bioorganic & medicinal chemistry letters》2011,21(9):2670-2674
Since the discovery of the dopamine D3 receptor, an intensive effort has been directed toward the development of potent and selective ligands in order to elucidate the function and potential therapeutic advantages of targeting D3 receptors. As a part of our efforts, a novel series of substituted benzolactams derivatives was synthesized mostly through palladium-catalyzed reactions. Their affinities on D1-D4 receptors were evaluated and the data led us to highly potent D3 ligands, some of them highly selective for D3 receptor, compared to the related dopamine receptor subtypes. Functional D3 activity assays of the most relevant compounds have been carried out revealing antagonist as well as partial agonist activity. 相似文献
3.
Compounds that target D2-like dopamine receptors (DRs) are currently used as therapeutics for several neuropsychiatric disorders including schizophrenia (antagonists) and Parkinson's disease (agonists). However, as the D2R and D3R subtypes are highly homologous, creating compounds with sufficient subtype-selectivity as well as drug-like properties for therapeutic use has proved challenging. This review summarizes the progress that has been made in developing D2R- or D3R-selective antagonists and agonists, and also describes the experimental conditions that need to be considered when determining the selectivity of a given compound, as apparent selectivity can vary widely depending on assay conditions. Future advances in this field may take advantage of currently available structural data to target alternative secondary binding sites through creating bivalent or bitopic chemical structures. Alternatively, the use of high-throughput screening techniques to identify novel scaffolds that might bind to the D2R or D3R in areas other than the highly conserved orthosteric site, such as allosteric sites, followed by iterative medicinal chemistry will likely lead to exceptionally selective compounds in the future. More selective compounds will provide a better understanding of the normal and pathological functioning of each receptor subtype, as well as offer the potential for improved therapeutics. 相似文献
4.
Abstract: This study investigated possible D1/D2 interactions in rat and bovine striatal tissue by examining the effects of D2 antagonists on the action of dopamine at D1 dopamine receptors. In addition, the extent to which D2 antagonists may induce an agonist low-affinity state of the D1 receptor was evaluated in comparison with the effects of the guanine nucleotide analogue 5′-guanylylimidodiphosphate [Gpp(NH)p]. In saturation experiments dopamine caused a dose-dependent decrease in rat striatal and bovine caudate D1 receptor density. This effect of dopamine, which has been shown to be sensitive to Gpp(NH)p, was not altered by pretreatment with either of the selective D2 antagonists eticlopride (200 nM) or domperidone (200 nM). Results from displacement experiments show that the affinity of dopamine for D1 receptors and the proportion of receptors in an agonist high-affinity state, are reduced by Gpp(NH)p (100 µM) but not by eticlopride. A molar excess of dopamine (100 µM) promotes the dissociation of (±)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol ([3H]SCH 23390) from rat striatal D1 receptors at a rate that is significantly slower than when dissociation is initiated using 1 µM piflutixol. After pretreatment with Gpp(NH)p, [3H]SCH 23390 dissociation induced by dopamine occurred at an even slower rate. Pretreatment with eticlopride had no effect on the dopamine-induced rate of [3H]SCH 23390 dissociation. These results indicate that all experimental approaches detected dopamine effects at D1 receptors that are Gpp(NH)p sensitive and D2 antagonist insensitive and provide no evidence to support a D1/D2 link operating at the receptor level. 相似文献
5.
Hiroo Maeno 《Molecular and cellular biochemistry》1982,43(2):65-80
Summary Physiological, pharmacological, histochemical and biochemical studies indicate that dopamine receptors are heterogenous in the, central nervous system with each individual functions. This review describes pharmacological and biochemical characteristics of dopamine receptors, particularly in canine caudate nucleus, which have been studied in our laboratory with a brief comparison to the current studies by other workers in similar research fields.Two distinct dopamine receptors have been characterized by means of [3H]dopamine binding to the synaptic membranes from canine caudate nucleus. One of the receptors with a Kd of about 3 M for dopamine may be associated with adenylate cyclase and referred to as D, receptor. The other receptor with a Kd of about 10 nM for dopamine is independent of adenylate cyclase and referred to as D2. A photochemical irreversible association of [3H]dopamine with the membraneous receptors makes it possible to separate D1 and D2 receptors from one another by gel filtration on a Sephadex G-200 column after solubilization with Lubrol PX. On the basis of selective inhibition of [3H]dopamine binding to D1 and D2 receptors, dopamine antagonists can be classified into three classes: D1-selective (YM-09151-2), D2-selective (sulpiride) and nonselective (haloperidol, chlorpromazine). Effects of these typical antagonists on the metabolism of rat brain dopamine suggest that D1 receptor is more closely associated with the neuroleptic-induced increase in dopamine turnover. Studies with 28 benzamide derivatives and some classical neuroleptics reveal that apomorphine-induced stereotypy displays a greater association with D1 than with D2 receptors.Dopamine-sensitive adenylate cyclase in canine caudate nucleus can be solubilized with Lubrol PX in a sensitive form to either dopamine, Gpp(NH)p or fluoride. Sephadex G-200 gel filtration separates adenylate cyclase from D1 receptors with a concomitant loss of dopamine sensitivity. Addition of the D1 receptor fraction to the adenylate cyclase restores the responsiveness to dopamine. The solubilized dopamine-unresponsive adenylate cyclase can be further separated into two distinct fractions by a batch-wise treatment with GTP-sepharose: a catalytic unit which does not respond to fluoride, and a guanine nucleotide regulatory protein. The regulatory protein confers distinct responsiveness to Gpp(NH)p and fluoride upon adenylate cyclase. These results indicate that dopamine-sensitive adenylate cyclase is composed of at least three distinct units; D1 receptor, guanine nucleotide regulatory protein and adenylate cyclase. 相似文献
6.
The function of the D3 dopamine (DA) receptor remains ambiguous largely because of the lack of selective D3 receptor ligands. To investigate the function and intracellular signaling of D3 receptors, we established a PC‐12/hD3 clone, which expresses the human D3 DA receptor in a DA producing cell line. In this model, we find that the D3 receptor functions as an autoreceptor controlling neurotransmitter secretion. Pre‐treatment with 3,6a,11, 14‐tetrahydro‐9‐methoxy‐2 methyl‐(12H)‐isoquino[1,2‐b] pyrrolo[3,2‐f][1,3] benzoxanzine‐1‐carboxylic acid, a D3 receptor preferring agonist, dose‐dependently suppressed K+‐evoked [3H]DA release in PC‐12/hD3 cells but not in the control cell line. This effect was prevented by D3 receptor preferring antagonists GR103691 and SB277011‐A. Furthermore, activation of D3 receptors significantly inhibits forskolin‐induced cAMP accumulation and leads to transient increases in phosphorylation of cyclin‐dependent kinase 5 (Cdk5), dopamine and cAMP‐regulated phosphoprotein of Mr 32 000 and Akt. Because we observed differences in Cdk5 phosphorylation as well as Akt phosphorylation after DA stimulation, we probed the ability of Cdk5 and phosphatidylinositol‐3 kinase (PI3K) to influence DA release. Cdk5 inhibitors, roscovitine, or olomoucine, but not the PI3K inhibitor wortmannin, blocked the D3 receptor inhibition of DA release. In a complimentary experiment, over‐expression of Cdk5 potentiated D3 receptor suppression of DA release. Pertussis toxin, 3‐[(2,4,6‐trimethoxyphenyl)methylidenyl]‐indolin‐2‐one and cyclosporine A also attenuated D3 receptor‐mediated inhibition of DA release indicating that this phenomenon acts through Gi/oα and casein kinase 1, and phosphatase protein phosphatase 2B (calcineurin), respectively. In support of previous data that D3 DA receptors reduce transmitter release from nerve terminals, the current results demonstrate that D3 DA receptors function as autoreceptors to inhibit DA release and that a signaling pathway involving Cdk5 is essential to this regulation. 相似文献
7.
Chen Yang Shun-Nan Ge Jia-Rui Zhang Lei Chen Zhi-Qiang Yan Li-Jun Heng Tian-Zhi Zhao Wei-Xin Li Dong Jia Jun-Ling Zhu Guo-Dong Gao 《PloS one》2013,8(6)
High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical–basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D1-like receptors or D2-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D2-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D2-like receptor antagonists. On the contrary, the selective dopamine D1-like receptor antagonist, , had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D2-like receptors, but not D1-like receptors, were involved in HVS regulation. This supports the important role of dopamine D2-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion. SCH23390相似文献
8.
Yunsheng Huang Robert R. Luedtke Rebekah A. Freeman Li Wu Robert H. Mach 《Bioorganic & medicinal chemistry》2001,9(12):7818
A series of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole derivatives was prepared and their affinity for dopamine D2 and D3 receptors was measured using in vitro binding assays. Several oxadiazole analogues were also prepared and tested for their affinity for dopamine D2 and D3 receptors. The results of receptor binding studies indicated that the incorporation of an imidazole moiety between the phenyl ring and the basic nitrogen did not significantly increase the selectivity for dopamine D3 receptors, whereas the incorporation of an oxadiazole at the same region resulted in a total loss of affinity for both dopamine receptor subtype binding sites. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinomethyl)imidazole (5i), which has a D3 receptor affinity of 21 nM and a 7-fold selectivity for D3 versus D2 receptors. The binding affinity for σ1 and σ2 receptors was also measured, and the results showed that several analogues were selective σ1 receptor ligands. 相似文献
9.
3H-spiroperidol bound in a saturable, stereospecifically displaceable manner to homogenates of bovine retina. Scatchard analysis of saturation experiments showed a KD of 1.35 nM and a density of binding sites of 107 fmoles · mg protein?1. Stereospecifically displaceable binding was pH and temperature dependent and linear with tissue concentration. Spiroperidol, pimozide, haloperidol and d-butaclamol were the most potent compounds in drug displacement curves (8.74 > pIC50 > 7.61 M). Other neuroleptics such as cisflupenthixol, fluphenazine, clozapine, chlorpromazine and pipamperone, were one order of magnitude less potent. Among dopamine agonists, apomorphine (pIC50 = 7.08 ± 0.19 M) was about 50 times more potent than dopamine itself, epinine and ADTN. Serotonin, α- and ß-adrenergic receptors agonists and antagonists were inactive. These results indicate that the sites labelled by 3H-spiroperidol in retina are dopaminergic; moreover the rank order of various antagonists and agonists observed in displacement curves suggests that this preparation could also provide a useful tool to reveal the selective affinity of drugs for the CNS dopamine receptor linked to the enzyme adenylylcyclase (D1-receptors). 相似文献
10.
《Life sciences》1995,56(15):PL285-PL290
The mechanism of the antinociceptive effect of buprenorphine was assessed by administering selective μ-, μ1-, δ- and κ-opioid receptor antagonists in mice. Intraperitoneal administration of buprenorphine, at doses of 0.3 to 3 mg/kg, produced dose-dependent antinociception in the tail-flick test. The antinociceptive activity of buprenorphine did not result from the activation of κ- or δ-opioid receptors, since treatment with either nor-binaltorphimine, a selective κ-opioid receptor antagonist, or naltrindole, a selective δ-opioid receptor antagonist, was completely ineffective in blocking buprenorphine-induced antinociception. However, the antinociceptive effect of buprenorphine was significantly antagonized by β-funaltrexamine, a selective μ-opioid receptor antagonist. Moreover, selective μ1-opioid receptor antagonists, naloxonazine and naltrexonazine, also significantly antagonized the antinociceptive effect of buprenorphine. Co-administration of κ- and δ-opioid receptor antagonists with the μ-opioid receptor antagonists had no significant effect on the antagonistic profiles of the μ-opioid receptor antagonists on the antinociceptive effect of buprenorphine. These results suggest that buprenorphine acts selectively at μ1-opioid receptors to induce antinociceptive effects in mice. 相似文献
11.
Nian Zhou Wayne Zeller Michael Krohn Herb Anderson Jun Zhang Emmanuel Onua Alex S. Kiselyov Jose Ramirez Guðrún Halldorsdottir Þorkell Andrésson Mark E. Gurney Jasbir Singh 《Bioorganic & medicinal chemistry letters》2009,19(1):123-126
A series of potent and selective EP3 receptor antagonists are described. Utilizing a pharmacophore model developed for the EP3 receptor, a series of 3,4-disubstituted indoles were shown to be high affinity ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors and are potent antagonists in functional assays. 相似文献
12.
The D2 dopamine receptor is an important therapeutic target for the treatment of psychotic, agitated, and abnormal behavioral states. To better understand the specific interactions of subtype‐selective ligands with dopamine receptor subtypes, seven ligands with high selectivity (>120‐fold) for the D4 subtype of dopamine receptor were tested on wild‐type and mutant D2 receptors. Five of the selective ligands were observed to have 21‐fold to 293‐fold increases in D2 receptor affinity when three non‐conserved amino acids in TM2 and TM3 were mutated to the corresponding D4 amino acids. The two ligands with the greatest improvement in affinity for the D2 mutant receptor [i.e., 3‐{[4‐(4‐iodophenyl) piperazin‐1‐yl]methyl}‐1H‐pyrrolo[2,3‐b]pyridine (L‐750,667) and 1‐[4‐iodobenzyl]‐4‐[N‐(3‐isopropoxy‐2‐pyridinyl)‐N‐methyl]‐aminopiperidine (RBI‐257)] were investigated in functional assays. Consistent with their higher affinity for the mutant than for the wild‐type receptor, concentrations of L‐750,667 or RBI‐257 that produced large reductions in the potency of quinpirole’s functional response in the mutant did not significantly reduce quinpirole’s functional response in the wild‐type D2 receptor. In contrast to RBI‐257 which is an antagonist at all receptors, L‐750,667 is a partial agonist at the wild‐type D2 but an antagonist at both the mutant D2 and wild‐type D4 receptors. Our study demonstrates for the first time that the TM2/3 microdomain of the D2 dopamine receptor not only regulates the selective affinity of ligands, but in selected cases can also regulate their function. Utilizing a new docking technique that incorporates receptor backbone flexibility, the three non‐conserved amino acids that encompass the TM2/3 microdomain were found to account in large part for the differences in intermolecular steric contacts between the ligands and receptors. Consistent with the experimental data, this model illustrates the interactions between a variety of subtype‐selective ligands and the wild‐type D2, mutant D2, or wild‐type D4 receptors. 相似文献
13.
Fabrizio Micheli Dieter Hamprecht Giorgio Bonanomi Romano Di Fabio Daniele Donati Gabriella Gentile Christian Heidbreder Adolfo Prandi Luca Tarsi Silvia Terreni 《Bioorganic & medicinal chemistry letters》2010,20(18):5491-5494
A new class of azabicyclo[3.1.0]benzenesulfonamides is presented as selective dopamine D3 antagonists together with SAR and selectivity data. 相似文献
14.
《Journal of receptor and signal transduction research》2013,33(1-4):329-339
AbstractChronic treatment with the D1 and D2 dopamine receptor antagonists SCH 23390 (0.5 mg/kg) and haloperidol decanoate (25 mg/kg) caused an up-regulation in D1 and D2 receptor densities, respectively, with no change in KD. Dopamine (20 μM) interacted with both receptor subtypes in a mixed competitive/non-competitive manner, causing a reduction in ligand binding affinity and an apparent decrease in receptor density. In the presence of dopamine, both vehicle-treated and SCH 23390-treated striatal preparations showed a significant loss in affinity for 3H-SCH 23390 binding to D1 receptors and a decrease in D1 receptor density of approximately 26%. Similarly, dopamine caused a substantial loss in 3H-spiperone binding affinity to D2 receptors and a 46% decrease in Bmax in both vehicle-treated and haloperidol-treated membranes. Thus, receptor up-regulation does not appear to alter the mode of interaction of dopamine with rat striatal dopamine receptors. 相似文献
15.
《Journal of receptor and signal transduction research》2013,33(3):131-147
Dopamine D4 receptors mediate a wide range of neuronal signal transduction cascades. Malfunctions of these mechanisms may contribute to the pathophysiology of neuropsychiatric disorders, and their modification underlies the actions of many psychotropic drugs. Postmortem neuropathological and genetic studies provide inconclusive associations between D4 receptors and schizophrenia. Clinical trials of partially selective lead D4 antagonists have proved them to be ineffective against psychotic symptoms in patients diagnosed with schizophrenia. However, associations are emerging between D4 receptors and other neuropsychiatric disorders, including attention-deficit hyperactivity disorder as well as specific personality traits such as novelty seeking. Preclinical studies indicate that D4 receptors play a pivotal role in the cellular mechanisms of hyperactivity, impulsivity, and working memory. Accordingly, D4 receptors have broader implications for human illnesses than has been suggested by early focus on psychotic illness as a clinical target, and selective D4 agents may yield clinically useful drugs for several neuropsychiatric disorders that require improved treatments. 相似文献
16.
Yuji Odagaki Masakazu Kinoshita Toshio Ota 《Journal of receptor and signal transduction research》2019,39(1):9-17
Although multiple roles of dopamine through D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptors are initiated primarily through stimulation or inhibition of adenylyl cyclase via Gs/olf or Gi/o, respectively, there have been many reports indicating diverse signaling mechanisms that involve alternative G protein coupling. In this study, dopamine-induced Gαq activation in rat brain membranes was investigated. Agonist-induced Gαq activation was assessed by increase in guanosine-5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding to Gαq determined by [35S]GTPγS binding/immunoprecipitation assay in rat brain membranes. Dopamine-stimulated Gαq functionality was highest in cortex as compared to hippocampus or striatum. In cerebral cortical membranes, this effect was mimicked by benzazepine derivatives with agonist properties at dopamine D1-like receptors, that is, SKF83959, SKF83822, R(+)-SKF81297, R(+)-SKF38393, and SKF82958, but not by the compounds with dopamine D2-like receptor agonist properties except for aripiprazole. Against expectation, stimulatory effects were also induced by SKF83566, R(+)-SCH23390, and pergolide. The pharmacological profiling by using a series of antagonists indicated that dopamine-induced response was mediated through dopamine D1-like receptor, which was distinct from the receptor involved in 5-HT-induced response (5-HT2A receptor). Conversely, the responses induced by SKF83566, R(+)-SCH23390, and pergolide were most likely mediated by 5-HT2A receptor, but not by dopamine D1-like receptor. Caution should be paid when interpreting the experimental data, especially in behavioral pharmacological research, in which SKF83566 or R(+)-SCH23390 is used as a standard selective dopamine D1-like receptor antagonist. Also, possible clinical implications of the agonistic effects of pergolide on 5-HT2A receptor has been mentioned. 相似文献
17.
Mark A. Hilfiker Ning Wang Xiaoping Hou Zhimin Du Mark A. Pullen Melanie Nord Rakesh Nagilla Harvey E. Fries Charlene W. Wu Anthony C. Sulpizio Jon-Paul Jaworski Dwight Morrow Richard M. Edwards Jian Jin 《Bioorganic & medicinal chemistry letters》2009,19(15):4292-4295
This Letter discloses a series of 2-aminothiadiazole amides as selective EP3 receptor antagonists. SAR optimization resulted in compounds with excellent functional activity in vitro. In addition, efforts to optimize DMPK properties in the rat are discussed. These efforts have resulted in the identification of potent, selective EP3 receptor antagonists with excellent DMPK properties suitable for in vivo studies. 相似文献
18.
Kashif Rashid William H. Baldridge Alexander K. Ball 《Journal of neurochemistry》1993,61(6):2025-2033
The possible existence of a dopamine D2 receptor-mediated regulation of dopamine release was investigated in the goldfish retina. Isolated retinas were preloaded with [3H]dopamine and superfused with D2 dopamine receptor agonists or antagonists to determine if there was an effect on [3H]dopamine release. The D2 receptor antagonist sulpiride increased both baseline [3H]- dopamine release and [3H]dopamine release induced by an increase in extracellular potassium concentration. The D2 receptor agonists LY-171555 and RU-24213 did not reduce baseline [3H]dopamine release but completely inhibited [3H]dopamine release induced by an increase in [K±]o. This action of the D2 agonists was blocked by sulpiride. These studies demonstrate the existence of D2 receptor, possibly autoreceptor, regulation of dopamine release in the teleost retina. 相似文献
19.
《Life sciences》1995,57(21):PL347-PL350
R(+)7-hydroxy-N,N-di-n-propyl-2-aminotetralin (R(+)-7-OH-DPAT), a selective dopamine D3 receptor agonist, (0.03–0.3 mg/Kg, S.c.) dose-relatedly caused emesis, whereas S (−)-7-OH-DPAT at even 1 mg/kg did not induce emesis in dogs. Apomorphine (0.03-0.3 mg/kg, s.c.) or quinpirole (0.03–0.1 mg/Kg, S.c.) also caused emesis in a dose-dependent manner. The potency of R(+)-7-OH-DPAT in inducing emesis was the same as that of apomorpine and quipirole. On the other hand, SKF-38393 (1 and 3 mg/Kg, S.c.), a selective d1 receptor agonist, failed to induce emesis in dogs. The emesis induced by R(+)-7-OH-DPAT (0.3 mg/Kg, S.c.) was inhibited by S(−)-eticlopride (0.01–0.1 mg/Kg, S.c.), a potent D2 and D3 receptor antagonist but not by SCH-23390 (1 mg/Kg, S.c.), a selective d1 receptor antagonist or clozapine (1 mg/Kg, S.c.), a D4 receptor antagonist. These results indicate that dopamine D3 receptors play an important role in the genesis of emesis in dogs. 相似文献
20.
《Journal of receptor and signal transduction research》2013,33(1):99-109
AbstractMammalian D1 and D2 dopamine receptors were stably expressed in Drosophila Schneider‐2 (S2) cells and screened for their pharmacological properties. Saturable, dose‐dependent, high affinity binding of the D1‐selective antagonist [3H]SCH‐23390 was detected only in membranes from S2 cells induced to express rat dopamine D1 receptors, while saturable, dose‐dependent, high affinity binding of the D2‐selective antagonist [3H]methylspiperone was detected only in membranes from S2 cells induced to express rat dopamine D2 receptors. No specific binding of either radioligand could be detected in membranes isolated from uninduced or untransfected S2 cells. Both dopamine D1 and D2 receptor subtypes displayed the appropriate stereoselective binding of enantiomers of the nonselective antagonist butaclamol. Each receptor subtype also displayed the appropriate agonist stereoselectivities. The dopamine D1 receptor bound the (+)‐enantiomer of the D1‐selective agonist SKF38393 with higher affinity than the (?)‐enantiomer, while the dopamine D2 receptor bound the (?)‐enantiomer of the D2‐selective agonist norpropylapomorphine with higher affinity than the (+)‐enantiomer. At both receptor subtypes, dopamine binding was best characterized as occurring to a single low affinity site. In addition, the low affinity dopamine binding was also found to be insensitive to GTPγS and magnesium ions. Overall, the pharmacological profiles of mammalian dopamine D1 and D2 receptors expressed in Drosophila S2 cells is comparable to those observed for these same receptors when they are expressed in mammalian cell lines. A notable distinction is that there is no evidence for the coupling of insect G proteins to mammalian dopamine receptors. These results suggest that the S2 cell insect G system may provide a convenient source of pharmacologically active mammalian D1 and D2 dopamine receptors free of promiscuous G protein contaminants. 相似文献