共查询到20条相似文献,搜索用时 203 毫秒
1.
BackgroundDopamine signaling is mediated by G s protein-coupled “D 1-like” receptors (D 1 and D 5) and G i-coupled “D 2-like” receptors (D 2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the G i-coupled dopamine D 2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the G s-coupled dopamine D 1-like receptor subtypes have never been identified on these cells. Activation of G s-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D 1-like receptor is expressed on ASM, and modulates its function through G s-coupling. MethodsThe mRNA and protein expression of dopamine D 1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D 1 receptor, HASM cells were treated with dopamine or the dopamine D 1-like receptor agonists ( {"type":"entrez-nucleotide","attrs":{"text":"A68930","term_id":"4759850","term_text":"A68930"}}A68930 or {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D 1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or {"type":"entrez-nucleotide","attrs":{"text":"A68930","term_id":"4759850","term_text":"A68930"}}A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BK Ca) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. ResultsMessenger RNA encoding the dopamine D 1 and D 5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D 1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D 1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D 1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D 1-like receptor antagonists {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 or {"type":"entrez-protein","attrs":{"text":"SCH39166","term_id":"1052842517","term_text":"SCH39166"}}SCH39166. {"type":"entrez-nucleotide","attrs":{"text":"A68930","term_id":"4759850","term_text":"A68930"}}A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. ConclusionsThese results demonstrate that the dopamine D 1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM. 相似文献
2.
D1-selective dopamine receptor agonists inhibit secretagogue-stimulated catecholamine secretion from bovine adrenal chromaffin cells. The purpose of the studies reported here was to use the radiolabeled D1-selective dopamine receptor antagonist, SCH23390, to characterize putative D1-like dopamine receptors responsible for this effect. Characterization of SCH23390 binding sites demonstrated an unusual pharmacological profile inconsistent with classical D1-like receptors. [ 125I]SCH23390 bound to adrenal medullary membranes was competed for by non-radioactive iodo-SCH23390 (Kd = 490 ± 50 nM), but not by (+)butaclamol. Other classical D1 antagonists had little, if any, effect. Competition with dopamine receptor agonists demonstrated a relative rank order of potency profile characteristic of D1-like dopamine receptors, however, K is were higher than those found in other tissues. The K is for competition of [ 125I]SCH23390 binding by C1-APB and SKF38393 (16 and 118 M, respectively) are nearly identical to the IC 50s previously observed for inhibition of secretion (9 and 100 M, respectively). Combined these data suggest that adrenal medullary membranes contain a novel SCH23390 binding site involved in the inhibition of secretion by D1-selective agonists. 相似文献
3.
The dopamine D 1, D 2, D 3 receptors, vesicular monoamine transporter type-2 (VMAT2), and dopamine transporter (DAT) densities were measured in 11 aged human brains (aged 77–107.8, mean: 91 years) by quantitative autoradiography. The density of D 1 receptors, VMAT2, and DAT was measured using [ 3H] {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390, [ 3H]dihydrotetrabenazine, and [ 3H]WIN35428, respectively. The density of D 2 and D 3 receptors was calculated using the D 3-preferring radioligand, [ 3H]WC-10 and the D 2-preferring radioligand [ 3H]raclopride using a mathematical model developed previously by our group. Dopamine D 1, D 2, and D 3 receptors are extensively distributed throughout striatum; the highest density of D 3 receptors occurred in the nucleus accumbens (NAc). The density of the DAT is 10–20-fold lower than that of VMAT2 in striatal regions. Dopamine D 3 receptor density exceeded D 2 receptor densities in extrastriatal regions, and thalamus contained a high level of D 3 receptors with negligible D 2 receptors. The density of dopamine D 1 linearly correlated with D 3 receptor density in the thalamus. The density of the DAT was negligible in the extrastriatal regions whereas the VMAT2 was expressed in moderate density. D 3 receptor and VMAT2 densities were in similar level between the aged human and aged rhesus brain samples, whereas aged human brain samples had lower range of densities of D 1 and D 2 receptors and DAT compared with the aged rhesus monkey brain. The differential density of D 3 and D 2 receptors in human brain will be useful in the interpretation of PET imaging studies in human subjects with existing radiotracers, and assist in the validation of newer PET radiotracers having a higher selectivity for dopamine D 2 or D 3 receptors. 相似文献
4.
Methamphetamine (METH) is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain—which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy) in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 µM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist) did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction. 相似文献
5.
AbstractChronic treatment with the D 1 and D 2 dopamine receptor antagonists SCH 23390 (0.5 mg/kg) and haloperidol decanoate (25 mg/kg) caused an up-regulation in D 1 and D 2 receptor densities, respectively, with no change in K D. 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 D 1 receptors and a decrease in D 1 receptor density of approximately 26%. Similarly, dopamine caused a substantial loss in 3H-spiperone binding affinity to D 2 receptors and a 46% decrease in B max 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
6.
We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH +) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl- p-tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH + neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH + neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH + neurons. A single i.p. injection of the D1 receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH + neurons after 4 days. Treatment with the D1-like receptor agonist {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH + neurons. At least the effects of {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 were prevented by a combined treatment with {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393. Immunohistochemical analysis indicated that striatal TH + neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH + neurons. The evidence that DHβE mimicked the action of {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 in increasing the number of TH + neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH + neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH + neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes. 相似文献
8.
We investigated the effect of methamphetamine (MA) injections on the circadian organization of behavior and individual tissues in the mouse. Scheduled, daily injections of MA resulted in anticipatory activity, with an increase in locomotor activity immediately prior to the time of injection. Daily MA also shifted the peak time of PER2 expression in the liver, pituitary, and salivary glands. It has been suggested that reward pathways, and dopamine signaling in particular, may underlie the effects of MA on the circadian system. To test this hypothesis, we examined the effect of the D1 receptor antagonist {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 (SCH) on circadian rhythms. The MA-induced shift in the phase of pituitary and salivary glands was attenuated by pretreatment with the D1 antagonist {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 (SCH). Interestingly, daily SCH, administered alone, also affected some circadian oscillators. The livers and lungs (but not pituitaries or salivary glands) of mice treated with daily injections of SCH displayed disrupted rhythms of PER2 expression, suggesting that D1 receptor signaling is important for entrainment of these organs. From these results, we conclude that MA has widespread effects within the circadian system, and that these effects are mediated, at least in part, by the dopaminergic system. This study also identifies a role for dopamine signaling in normal entrainment of circadian oscillators. 相似文献
9.
Dopamine (DA), a neurotransmitter in the nervous system, has been shown to modulate immune function. We have previously reported that five subtypes of DA receptors, including D1R, D2R, D3R, D4R and D5R, are expressed in T lymphocytes and they are involved in regulation of T cells. However, roles of these DA receptor subtypes and their coupled signal-transduction pathway in modulation of natural killer (NK) cells still remain to be clarified. The spleen of mice was harvested and NK cells were isolated and purified by negative selection using magnetic activated cell sorting. After NK cells were incubated with various drugs for 4 h, flow cytometry measured cytotoxicity of NK cells against YAC-1 lymphoma cells. NK cells expressed the five subtypes of DA receptors at mRNA and protein levels. Activation of D1-like receptors (including D1R and D5R) with agonist {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393 enhanced NK cell cytotoxicity, but activation of D2-like receptors (including D2R, D3R and D4R) with agonist quinpirole attenuated NK cells. Simultaneously, {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393 elevated D1R and D5R expression, cAMP content, and phosphorylated cAMP-response element-binding (CREB) level in NK cells, while quinpirole reduced D3R and D4R expression, cAMP content, and phosphorylated CREB level in NK cells. These effects of {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393 were blocked by {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390, an antagonist of D1-like receptors, and quinpirole effects were abolished by haloperidol, an antagonist of D2-like receptors. In support these results, H89, an inhibitor of phosphokinase A (PKA), prevented the {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393-dependent enhancement of NK cells and forskolin, an activator of adenylyl cyclase (AC), counteracted the quinpirole-dependent suppression of NK cells. These findings show that DA receptor subtypes are involved in modulation of NK cells and suggest that D1-like receptors facilitate NK cells by stimulating D1R/D5R-cAMP-PKA-CREB signaling pathway and D2-like receptors suppress NK cells by inhibiting D3R/D4R-cAMP-PKA-CREB signaling pathway. The results may provide more targets of therapeutic strategy for neuroimmune diseases. 相似文献
10.
The mesencephalic dopamine (DA) system is the main DA system related to affective and cognitive functions. The system consists of two different cell groups, A9 and A10, which originate from different regions of the midbrain. The striatum is the main input from the midbrain, and is functionally organized into associative, sensorimotor and limbic subdivisions. At present, there have been few studies investigating the associations of DA functions between striatal subdivisions and extrastriatal regions. The aim of this study was to investigate the relationship of DA D 1 receptor (D 1R) expression between striatal subdivisions and extrastriatal regions in humans using positron emission tomography (PET) with voxel-by-voxel whole brain analysis. The PET study was performed on 30 healthy subjects using [ 11C] {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 to measure D 1R expression. Parametric images of binding potentials ( BP
ND) were created using the simplified reference tissue model. Regions of interest were defined for striatal subdivisions. Multiple regression analysis was undertaken to determine extrastriatal regions that were associated with each striatal subdivision in BP
ND using statistical parametric mapping 5. The BP
ND values of associative, sensorimotor and limbic subdivisions were similarly correlated with those of multiple brain regions. Regarding the interrelationships among striatal subdivisions, mutual correlations were found among associative, sensorimotor and limbic subdivisions in BP
ND as well. The relationships in BP
ND between striatal subdivisions and extra-striatal regions suggest that differential striatal subdivisions and extrastriatal regions have a similar biological basis of D 1R expression. Different DA projections from the midbrain did not explain the associations between striatal subdivisions and extrastriatal regions in D 1R expression, and the DA-related neural networks among the midbrain, striatum and the other regions would contribute to a similar D 1R expression pattern throughout the whole brain. 相似文献
11.
Abstract: This study investigated possible D 1/D 2 interactions in rat and bovine striatal tissue by examining the effects of D 2 antagonists on the action of dopamine at D 1 dopamine receptors. In addition, the extent to which D 2 antagonists may induce an agonist low-affinity state of the D 1 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 D 1 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 D 2 antagonists eticlopride (200 n M) or domperidone (200 n M). Results from displacement experiments show that the affinity of dopamine for D 1 receptors and the proportion of receptors in an agonist high-affinity state, are reduced by Gpp(NH)p (100 µ M) but not by eticlopride. A molar excess of dopamine (100 µ M) promotes the dissociation of (±)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1 H-3-benzazepine-7-ol ([ 3H]SCH 23390) from rat striatal D 1 receptors at a rate that is significantly slower than when dissociation is initiated using 1 µ M 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 D 1 receptors that are Gpp(NH)p sensitive and D 2 antagonist insensitive and provide no evidence to support a D 1/D 2 link operating at the receptor level. 相似文献
12.
Renal dopamine D 1-like receptors (D 1R and D 5R) and the gastrin receptor (CCK BR) are involved in the maintenance of sodium homeostasis. The D 1R has been found to interact synergistically with CCK BR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D 5R, which has a higher affinity for dopamine than D 1R, has some constitutive activity. Hence, we sought to investigate the interaction between D 5R and CCK BR in the regulation of renal sodium excretion. In present study, we found D 5R and CCK BR increase each other’s expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D 5R and CCK BR and in RPT cells from a male normotensive human. The specificity of D 5R in the D 5R and CCK BR interaction was verified further using a selective D 5R antagonist, LE-PM436. Also, D 5R and CCK BR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCK BR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs) is greater in D 5R -/- mice than D 5R +/+ littermates and D 5R protein expression in PMFs is also greater in CCK BR -/- mice than CCK BR +/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCK BR and D 5R proteins in PMFs. Disruption of CCK BR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCK BR antagonist and {"type":"entrez-protein","attrs":{"text":"Sch23390","term_id":"1052733334"}}Sch23390, a D 1R/D 5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by {"type":"entrez-protein","attrs":{"text":"Sch23390","term_id":"1052733334"}}Sch23390 while the natriuresis caused by fenoldopam, a D 1R/D 5R agonist, was blocked by YF476. Taken together, our findings indicate that CCK BR and D 5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake. 相似文献
13.
AbstractThe interaction of SCH 23390 with dopamine (DA) and serotonin (5-HT) systems has been examined in vivo and in vitro. Like selective 5-HT 2 blockers, SCH 23390 inhibited in vivo [ 3H]spiperone binding in the rat frontal cortex (ID 50: 1.5 mg/kg) without interacting at D 2 sites. SCH 23390 was equipotent to cinanserin and methysergide. In vitro, SCH 23390 inhibited [ 3H]ketanserin binding to 5-HT 2 sites (IC 50 = 30 nM). Biochemical parameters linked to DA and 5-HT were not changed excepted in striatum where SCH 23390 increased HVA and DOPAC. In the L-5-HTP syndrome model, SCH 23390 clearly showed antagonism of 5-HT 2 receptors. SCH 23390 had weak affinity for 5-HT 1B (IC 50 = 0.5 μM), 5-HT 1A (IC 50 = 2.6 μM) and α; 1-adenergic receptors (IC 50 = 4.4 μM). 相似文献
14.
Although multiple roles of dopamine through D 1-like (D 1 and D 5) and D 2-like (D 2, D 3, and D 4) receptors are initiated primarily through stimulation or inhibition of adenylyl cyclase via G s/olf or G i/o, respectively, there have been many reports indicating diverse signaling mechanisms that involve alternative G protein coupling. In this study, dopamine-induced Gα q activation in rat brain membranes was investigated. Agonist-induced Gα q activation was assessed by increase in guanosine-5′- O-(3-[ 35S]thio)triphosphate ([ 35S]GTPγS) binding to Gα q determined by [ 35S]GTPγS binding/immunoprecipitation assay in rat brain membranes. Dopamine-stimulated Gα q 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 D 1-like receptors, that is, SKF83959, SKF83822, R(+)-SKF81297, R(+)-SKF38393, and SKF82958, but not by the compounds with dopamine D 2-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 D 1-like receptor, which was distinct from the receptor involved in 5-HT-induced response (5-HT 2A receptor). Conversely, the responses induced by SKF83566, R(+)-SCH23390, and pergolide were most likely mediated by 5-HT 2A receptor, but not by dopamine D 1-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 D 1-like receptor antagonist. Also, possible clinical implications of the agonistic effects of pergolide on 5-HT 2A receptor has been mentioned. 相似文献
15.
Dopaminergic compounds affect gastric secretion and response to experimental gastric mucosal injury. We showed previously that the novel dopamine D 4 receptor antagonist, clozapine, significantly reduces gastric acid secretion and restraint stress-induced gastric lesions. Because the selectivity of clozapine for D 4 receptors has recently been questioned, we tested the ability of a known d 1 receptor blocker, SCH23390, to affect clozapine-induced reduction in gastric acid secretion. SCH23390 given i.p. or i.c.v., at doses that did not affect gastric acid secretion, significantly blocked the anti-secretory effect of clozapine, administered either peripherally or centrally. These data suggest that neither clozapine nor SCH23390 exhibit as high a degree of selectivity for the dopamine D 4 and d 1 receptor, respectively, as previously believed. 相似文献
16.
Central regulatory mechanisms for food intake regulation vary among animals. Evidence from animal studies suggests central opioids and dopamine have prominent role on appetite regulation but their interaction(s) have not been studied in layer-type chicken. Thus, in this study six experiments designed to investigate intracerebroventricular (ICV) administration of SCH23390 (D 1 like receptors antagonist), Sulpride (D 2 like receptors antagonist), DAMGO (μ-opioid receptors agonist), DPDPE (δ-opioid receptors agonist), U-50488H (κ-opioid receptors agonist) on feeding behavior in 3 h food deprived neonatal layer-type chickens. In experiment 1, chicks ICV injected with control solution, SCH23390 (2.5 nmol), DAMGO (125 pmol) and their combination (SCH23390 + DAMGO). In experiment 2: control solution, SCH23390 (2.5 nmol), DPDPE (δ-opioid receptors agonist, 40 pmol) and SCH23390 + DPDPE were applied to the birds. In experiment 3, injections were control solution, SCH23390 (2.5 nmol), U-50488H (30 nmol) and SCH23390 + U-50488H. In experiments 4–6 were similar to experiments 1–3 except Sulpride (2.5 nmol) applied instead of SCH23390. Then, cumulative food intake was recorded until 120 min after injection. According to the results, ICV injection of DAMGO (125 pmol) significantly decreased food intake but co-injection of DAMGO + SCH23390 diminished DAMGO-induced hypophagia ( P < 0.05). Also, SCH23390 was not able to decrease the DPDPE- and U-50488H-induced hyperphagia ( P > 0.05). Furthermore, Sulpride had no role on DAMGO, DPDPE and U-50488H-induced food intake ( P > 0.05). These results suggest there is an interaction between opioidergic and dopaminergic systems via μ and D 1 receptors in appetite regulation in chicken. 相似文献
17.
Dopamine is able to inhibit the epinephrine-induced aggregation of human blood platelets, but the mechanism of action has not been elucidated. In this study we report that membranes from human blood platelets possess high affinity, saturable and stereoselective binding sites for the D1 dopamine receptor antagonist (3H) SCH 23390. (3H) SCH 23390 appeared to label a single class of binding sites with a Bmax of 18.6 +/- 1.6 fmol/mg protein and a KD of 0.8 nM. The potencies of different dopaminergic antagonists and agonists in displacing (3H) SCH 23390 from blood platelet membranes were similar to those obtained for striatal membranes. Unlike the classically defined D1 receptors, e.g. those in striatum, the D1 receptor sites on platelets appeared not to be coupled to the adenylate cyclase system, hence the term "D1-like". The D1 agonist SKF 38393 was more potent than dopamine in inhibiting platelet aggregation induced by epinephrine, and the effects of dopamine and SKF 38393 were prevented by SCH 23390. These results suggest that the inhibitory action of dopamine on the epinephrine-induced platelet aggregation is mediated through these D1-like receptors. 相似文献
18.
Cannabidiol (CBD) is a non-psychotomimetic compound with strong potential to decrease the psychostimulant’s rewarding effect with unclear receptors. Furthermore, as a part of the reward circuit, the hippocampus plays a crucial role in regulating the reward properties of drugs as determined by conditioned place preference (CPP). In the current research, CPP was used to evaluate the role of intra-CA1 microinjection of D1-like dopamine receptor antagonists in CBD's inhibitory effect on the acquisition and expression phases of methamphetamine (METH). Animals were treated by METH (1 mg/kg; sc) in a five-day schedule to induce CPP. To find out the impact of D1-like dopamine receptor antagonist, SCH23390, in the CA1 on the inhibitory influence of CBD on the acquisition of METH, the rats received intra-CA1 administration of SCH23390 (0.25, 1, and 4 µg/0.5 µl) following ICV treatment of CBD (10 µg/5 µl) over conditioning phase of METH. Furthermore, animals were given SCH23390 in the CA1 ensuing ICV microinjection of CBD (50 µg/5 µl) in the expression phase of METH to rule out the influence of SCH23390 on the suppressive effect of CBD on the expression of METH CPP. Intra-CA1 microinjection of SCH23390 abolished CBD's suppressive impact on both METH-induced CPP phases without any side effect on the locomotion. The current research disclosed that CBD inhibited the rewarding characteristic of METH via D1-like dopamine receptors in the CA1 region of the hippocampus. 相似文献
19.
A series of novel benzazepine derived dopamine D 1 antagonists have been discovered. These compounds are highly potent at D 1 and showed excellent selectivity over D 2 and D 4 receptors. SAR studies revealed that a variety of functional groups are tolerated on the D-ring of known tetracyclic benzazepine analog 2, SCH 39166, leading to compounds with nanomolar potency at D 1 and good selectivity over D 2-like receptors. 相似文献
20.
Abstract: To assess the importance of the cysteine residues Cys 347 and Cys 351 in the carboxylic tail in the human D 1 dopamine receptor, seven mutant receptors were constructed by PCR. The pharmacological and functional properties of the wild-type and mutant receptors were assessed following transient expression in COS-7 cells. Affinities for [ 3H]SCH 23390 of mutant S347 (Cys 347→ Gly), T348 (Tyr 348→ stop), S351 (Cys 351→ Gly), T351 (Cys 351→ stop), T352 (Pro 352→ stop), and S347/S351 (Cys 347→ Gly and Cys 351→ Gly) were similar to that of wild-type receptor, whereas the expression levels were reduced up to 80%. The potency of dopaminergic antagonists for these mutant receptors was very similar to that of the wild-type receptor. However, mutant T347 (Cys 347→ stop) showed a 15–25-fold reduced affinity for the antagonists SCH 23390, (+)-butaclamol, and cis-flupentixol, thus not allowing radioligand analysis. Wild-type and mutant receptors responded dose-dependently with similar potency to dopamine and SKF 38393 with an increased adenylyl cyclase activity. However, mutant receptors with the Cys 347 residue changed or removed displayed a diminished ability to activate adenylyl cyclase. Dopamine preexposure desensitized wild-type and mutant S351 receptors. However, mutant receptors with Cys 347 replaced or the distal part of the carboxyl tail removed were unable to desensitize. Thus, Cys 347 in the cytoplasmic tail of the human D 1 dopamine receptor is important for the receptor in maintaining the conformation for antagonist binding, to play a crucial role in activation of adenylyl cyclase, and to be essential for agonist-induced desensitization. 相似文献
|