Biomedical subjects

Zheng Wang

Publications and source records attributed to Zheng Wang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Inducible resistance of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand receptor 2-mediated apoptosis by generation of a blockade at the death domain function.

Induction of tumor cell resistance to therapeutics has been a major obstacle in cancer therapy. Targeting of the death receptors by a natural ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or agonistic monoclonal antibodies against TRAIL receptor 1 (TRAIL-R1) or TRAIL receptor 2 (TRAIL-R2) has been thought to be a promising cancer therapy. To determine whether tumor cells are able to generate a resistance to apoptosis induced by an anti-TRAIL-R2 antibody, TRA-8, we examined the apoptotic response of human breast and ovarian cancer cell lines after treatment with TRA-8. Our results show that tumor cell resistance to TRA-8 can be induced by repeated treatment of tumor cells with low, non-apoptosis-inducing doses of TRA-8. Interestingly, the induced resistance to apoptosis was not due to a global apoptotic defect in tumor cells but rather a selective defect in the TRAIL-R2 signaling pathway. Whereas TRA-8-treated tumor cells developed a selective resistance to TRAIL-R2-mediated apoptosis, the apoptotic responses induced by TRAIL, an anti-TRAIL-R1 antibody (2E12), and other apoptotic stimuli were not impaired. The expression levels of cell surface TRAIL-R2 were not altered and mutations of TRAIL-R2 were not found in the resistant cells. The induced TRA-8 resistance was due to a selective blockade at the level of the death domain and could be reversed by a wide array of chemotherapeutic agents. Proteomic analysis of death-inducing signaling complex formation during TRA-8 treatment shows that the translocation of TRAIL-R2-associated apoptotic proteins was significantly altered. Our results suggest that the prevention of tumor cell resistance to therapeutic agents that target the death receptors must be taken into consideration.

Apoptosis↗

PubMed2006

Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells.

The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D(3) dopamine receptor gene in mice produces renin-dependent hypertension. In rats, D(2)-like receptors reduce angiotensin II binding sites in renal proximal tubules (RPTs). Because the major D(2)-like receptor in RPTs is the D(3) receptor, we examined whether D(3) receptors regulate angiotensin II type 1 (AT(1)) receptors in rat RPT cells. The effect of D(3) receptors on AT(1) receptors was studied in vitro and in vivo. The D(3) receptor agonist PD128907 decreased AT(1) receptor protein and mRNA in WKY RPT cells and increased it in SHR cells. PD128907 increased D(3) receptors in WKY cells but had no effect in SHR cells. D(3)/AT(1) receptors colocalized in RPT cells; D(3) receptor stimulation decreased the percent amount of D(3) receptors that coimmunoprecipitated with AT(1) receptors to a greater extent in WKY than in SHR cells. However, D(3) receptor stimulation did not change the percent amount of AT(1) receptors that coimmunoprecipitated with D(3) receptors in WKY cells and markedly decreased the coimmunoprecipitation in SHR cells. The D(3) receptor also regulated the AT(1) receptor in vivo because AT(1) receptor expression was increased in kidneys of D(3) receptor-null mice compared with wild type littermates. D(3) receptors may regulate AT(1) receptor function by direct interaction with and regulation of AT(1) receptor expression. One mechanism of hypertension may be related to increased renal expression of AT(1) receptors due decreased D(3) receptor regulation.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

[Safety and efficacy of resection of hemivertebrae by posterior approach in treatment of thoracolumbar kyphoscoliosis in adolescents].

OBJECTIVE: To investigate the safety and efficacy of resection of hemivertebrae by posterior approach in treatment of thoracolumbar kyphoscoliosis in adolescents. METHODS: twenty-eight patients of kyphoscoliosis, 19 male and 9 female, aged 12 approximately 16, 12 cases with the hemivertebra located in T(12), 10 cases in L(1), and 6 cases in T(11), and with a mean angle of 75 degrees in kyphosis and 48 degrees in scoliosis by the Cobb measurement, underwent resection of the hemivertebrae via the posterior approach and were followed up for 3.5 years. RESULTS: The mean surgical time was 3.7 hours and the average blood loss was 900 ml. Intercostal neuralgia occurred in one patient and relieved automatically without treatment. Hemothorax and pneumothorax were found in two cases during the operation and were healed after 1 week. Solid fusion was obtained in all the patients. The Cobb measurement was 19 degrees in kyphosis and 14 degrees in scoliosis on average at the final follow-up. No neurological deficit and infection was noted in the late stage. Clinically, no spinal imbalance or trunk shift was observed in all patients. CONCLUSION: Resection of hemivertebrae via posterior approach is safe and effective in the treatment of thoracolumbar kyphoscoliosis in adolescents.

Adolescent↗

PubMed2006

Self-supported chiral catalysts for heterogeneous enantioselective reactions.

The development of heterogeneous chiral catalysts for enantioselective reactions is highly desirable in order to overcome some drawbacks of homogeneous catalysts. Different from the conventional approaches by using various types of supports or biphasic systems for the recovery and reuse of homogeneous catalysts, a conceptually new strategy for heterogenization of homogeneous chiral catalysts, that is, a "self-supporting" approach, has been developed to use homochiral metal-organic coordination polymers generated by the self-assembly of chiral multitopic ligands with metal ions, and thus obviates the use of any support. In this concept article, the success of this "self-supporting" strategy will be exemplified in heterogeneous catalysis of asymmetric carbonyl-ene, sulfoxidation, epoxidation, and asymmetric hydrogenation reactions.

Catalysis↗

PubMed2006

Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation.

The functional spatial resolution in most of hemodynamics-based functional neuroimaging techniques is limited by the fineness of hemodynamic control with the active vascular beds likely at submillimeter resolution. This study was designed to visualize changes of cerebral blood flow (CBF) at submillimeter spatial scale on the prolonged isoflurane-anesthetized rats model by using laser speckle contrast imaging (LSCI) technique. Recently, this old method has attracted an increasing interest in studies of brain activities under normal and pathophysiologic conditions. However, some paramount assumptions behind this imaging technique have been kept ignored in this field since 1981 firstly proposed by Fercher and Briers. Most recently, these assumptions are claimed as serious mistakes that made LSCI fail to reproducibly and correctly measure blood flow speed. In our study, these issues are also re-examined theoretically and re-evaluated experimentally based on the results from the classical carbon dioxide challenge model. The detailed distribution of CBF responses to the stimulation induced by different levels of carbon dioxide pressure was obtained with tens of micron spatial resolution. The relative CBF images over the exposed cortical area acquired by LSCI were also compared with laser-Doppler measurements. Our results show that these assumptions would not produce any significant errors on investigating changes of blood flow and also achieve high specificity to assess cerebral microcirculation, as would facilitate its broad application in functional imaging field.

Algorithms↗

PubMed2006

[Inhibition of growth and metastasis of hepatocellular carcinoma by rapamycin: experiment with mice].

OBJECTIVE: To investigate the effects of rapamycin (RPM) in inhibiting the growth and metastasis of hepatocellular carcinoma (HCC). METHODS: Human HCC cells of the line MHCC97H with a high potential of metastasis were divided into 3 groups to be cultured with cyclosporine A (CsA) 100 ng/ml, RPM 10 ng/ml, or CsA + RPM for 48 hours. Flow cytometry was used to examine the apoptosis and cell cycle MTT method was used to examine the effect of RMP on the proliferation of the MHCC97H cells. RT-PCR was used to detect the mRNA expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hypoxia-inducible factor-1alpha (HIF-1alpha), and transforming growth factor b (TGFb). Another MHCC97H cells were cultured in complete medium without RPM for 48 hours, then the protein expression of VEGF in the supernatant was detected by ELISA. Twenty-eight nude LCI-D20 mice were inoculated with human HCC cells and then divided into 4 groups to be fed with CsA (25 mg/kg), RPM (2 mg/kg), CsA + RPM, and normal saline (0.2 ml, as control group) for 35 days. Then the mice were killed to take the weight of inoculated tumor, measure the blood drug concentration, calculate the lung metastasis rate and number of metastatic foci, and observe pathology of the lung. RESULTS: CsA showed no effect on the cycle of the MHCC97H cells. The MHCC97H cells of the RPM and CsA + RPM groups arrested at the stage G(0)/G(1) (both P = 0.000). MMT method also showed that the proliferation of the MHCC97H cells in the RPM and CsA + RPM groups were blocked (P = 0.003 and P = 0.002). However, CsA did not influence the proliferation of the MHCC97H cells. Flow cytometry showed that RPM did not promote the apoptosis of the MHCC97H cells. RT-PCR showed that RPM down-regulated the mRNA expression of VEGF and HIF-1alpha (both P < 0.05), however, did not influence the mRNA expression of bFGF, TGFb, and TGFb. The VEGF protein level in the supernatant of the culture fluid of MHCC97H cells of the RPM group was (890.3 +/- 25.1) pg/ml, significantly lower than that of the control group, (1583.7 +/- 17.3) pg/ml (P = 0.000). The tumor inhibiting rate of the RPM group was 63.7%, not significantly different from that of the RPM + CsA group (80.9%, P = 1.000). The metastatic rate of the CsA and control groups were both 100% with a higher number of metastatic tumors in the CsA group (P = 0.046). CONCLUSION: RPM significantly inhibits the growth and metastasis of HCC. RPM-based immunosuppressive regimen may be of value in HCC patients receiving liver transplantation.

Animals↗

PubMed2006

Regenerative adsorption and removal of H2S from hot fuel gas streams by rare earth oxides.

Sorbent materials that allow for high-temperature, regenerative desulfurization of fuel gas streams for the anode of a solid oxide fuel cell have been developed. Reversible adsorption of H2S on cerium and lanthanum oxide surfaces is demonstrated over many cycles at temperatures as high as 800 degrees C, on both fresh or presulfided sorbents, and at very high space velocities. The adsorption and desorption processes are very fast, and removal of H2S to sub-parts per million levels is achieved at very short (millisecond) contact times. Any type of sulfur-free gas, including water vapor, can be used to regenerate the sorbent surface. Preferably, the anode off-gas stream is used to sweep the desorbed H(2)S to a burner.

Journal Article↗

PubMed2006

Subunit exchange of MjHsp16.5 studied by single-molecule imaging and fluorescence resonance energy transfer.

MjHsp16.5 was separately labeled by fluorescent dye Cy3 and Cy5.5. The dissociation event of a single 24-mer MjHsp16.5 molecule was captured by single-molecule imaging (SMI). Temperature-regulated subunit exchange was revealed by the real-time fluorescence resonance energy transfer (FRET). The combination of single-molecular statistics and kinetic parameters from FRET experiments leads to the conclusion that below 75 degrees C the rate-determining step of the subunit exchange was the dissociation of the dye-labeled 24-mer in which the dimer was intact, whereas above 75 degrees C, smaller units emerged in the exchange and the rate-determining step had the character of a bimolecular reaction.

Archaeal Proteins↗

PubMed2006

Evolution of helotialean fungi (Leotiomycetes, Pezizomycotina): a nuclear rDNA phylogeny.

The highly divergent characters of morphology, ecology, and biology in the Helotiales make it one of the most problematic groups in traditional classification and molecular phylogeny. Sequences of three rDNA regions, SSU, LSU, and 5.8S rDNA, were generated for 50 helotialean fungi, representing 11 out of 13 families in the current classification. Data sets with different compositions were assembled, and parsimony and Bayesian analyses were performed. The phylogenetic distribution of lifestyle and ecological factors was assessed. Plant endophytism is distributed across multiple clades in the Leotiomycetes. Our results suggest that (1) the inclusion of LSU rDNA and a wider taxon sampling greatly improves resolution of the Helotiales phylogeny, however, the usefulness of rDNA in resolving the deep relationships within the Leotiomycetes is limited; (2) a new class Geoglossomycetes, including Geoglossum, Trichoglossum, and Sarcoleotia, is the basal lineage of the Leotiomyceta; (3) the Leotiomycetes, including the Helotiales, Erysiphales, Cyttariales, Rhytismatales, and Myxotrichaceae, is monophyletic; and (4) nine clades can be recognized within the Helotiales.

Ascomycota↗

PubMed2006

Magnetic bead-based solid phase for selective extraction of genomic DNA.

Magnetic bead-based solid phases are widely used for the separation of nucleic acids from complex mixtures. The challenge to selectively separate specific DNA molecules (via complementary hybridization) in a single step is the selection of a linker between the capture probe and the solid support that can be exposed to high temperatures in the presence of a high salt media. This article presents a general platform for the fabrication of a magnetic bead-based selective solid phase that can be used for subtractive hybridization or sequence capture applications. Phosphorus dendrimers are used for the first time as linkers in a magnetic bead-based selective solid phase for capture of genomic DNA. Aside from providing a high loading capacity, they render a stable bond between the capture probe and the surface under the high temperature and salt conditions required for denaturation and capture to proceed in a single step. The thermal stability of the solid phase under these conditions is first demonstrated by hybridizing a Cy3-labeled target. The selective capture of DNA targets in a single step is then demonstrated by subtractive hybridization of fragmented human genomic DNA. The specificity and selectivity of the solid phase are demonstrated by the recovery of adenovirus serotype 4 DNA spiked into the human DNA target. The effect of steric and electrostatic constraints was also investigated by using dendrimers of different generations that vary in their size and the number of branches. The results demonstrate that this platform can be used for single-step subtractive hybridization applications with better performance over the conventional two-step method using streptavidin-coated magnetic beads.

Adenoviridae↗

PubMed2006

Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience.

AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune, rapamycin) in a consecutive cohort of 248 liver allograft recipients. METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n = 7) after OLT. RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable. CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

Adaptor Proteins, Signal Transducing↗

PubMed2006

[Analysis of the risk factors influencing the prognosis of orthotopic liver transplantation for hepatocellular carcinoma and summary of relevant clinical experience].

OBJECTIVE: To analyze the risk factors influencing the prognosis of orthotopic liver transplantation for hepatocellular carcinoma (HCC) and sum up the relevant clinical experience in diagnosis and treatment of HCC. METHODS: The clinical data of 198 HCC patients, 177 males and 21 females, aged 49 (24-83), were analyzed. RESULTS: The 0.5-, 1-, and 2-year survival rates were 89%, 78%, and 65 respectively. The rates of disease-free survival (DFS) were 85%, 73, and 67% respectively. Univariate analysis revealed that tumor size, presence of vascular invasion, Edmondson grade, TNM classification, and preoperative alpha-fetoprotein (AFP) were significantly related to DFS, and the 4 foregoing factors were also related to the survival rate. Cox regression analysis suggested that presence of vascular invasion was an independent prognostic factor of survival rate and DFS. CONCLUSION: Vascular invasion plays a leading role in evaluating the prognosis of orthotopic liver transplantation for HCC. It is important to discover the micro-metastasis and explore more effective approaches to prevent recurrence after transplantation.

Adult↗

PubMed2006

Experimental and theoretical studies on the hydrogen-bond-promoted enantioselective hetero-Diels-Alder reaction of Danishefsky's diene with benzaldehyde.

The enantioselective hetero-Diels-Alder (HDA) reaction of Danishefsky's diene with benzaldehyde has been achieved catalytically by a series of alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL) derivatives through hydrogen-bonding activation, affording 2-phenyl-2,3-dihydro-4H-pyran-4-one after trifluoroacetic acid workup in moderate yield and good enantioselectivity. The alpha,alpha'-aryl substituents in the TADDOL molecules are found to exert a significant impact on both the activity and the enantioselectivity of the catalysis. In combination with the experimental investigations, the mechanism of the present reaction has also been studied theoretically using the ONIOM (B3LYP/6-31G:PM3) method with trans-1,3-dimethoxy-1,3-butadiene as the model for Danishefsky's diene. In agreement with the experimental findings, the calculation results indicate that this TADDOL-catalyzed HDA reaction proceeds via a concerted mechanism through an asynchronous and zwitterionic transition structure (TS). The carbonyl group of benzaldehyde is activated by forming an intermolecular hydrogen bond with one of the hydroxy groups of TADDOL. Meanwhile, the intramolecular hydrogen bond between the two hydroxy groups in TADDOL is found to facilitate the intermolecular hydrogen bonding with benzaldehyde. The sense of asymmetric induction is well-rationalized by the analysis of the relative energies of TADDOL-complexed TSs, while the different stereocontrol capabilities exhibited by TADDOLs in the reaction can be qualitatively established on the basis of the structural features of their corresponding TSs.

Alkenes↗

PubMed2006

Control of petal shape and floral zygomorphy in Lotus japonicus.

Zygomorphic flowers, with bilateral (dorsoventral) symmetry, are considered to have evolved several times independently in flowering plants. In Antirrhinum majus, floral dorsoventral symmetry depends on the activity of two TCP-box genes, CYCLOIDEA (CYC) and DICHOTOMA (DICH). To examine whether the same molecular mechanism of floral asymmetry operates in the distantly related Rosid clade of eudicots, in which asymmetric flowers are thought to have evolved independently, we investigated the function of a CYC homologue LjCYC2 in a papilionoid legume, Lotus japonicus. We showed a role for LjCYC2 in establishing dorsal identity by altering its expression in transgenic plants and analyzing its mutant allele squared standard 1 (squ1). Furthermore, we identified a lateralizing factor, Keeled wings in Lotus 1 (Kew1), which plays a key role in the control of lateral petal identity, and found LjCYC2 interacted with Kew1, resulting in a double mutant that bore all petals with ventralized identity to some extents. Thus, we demonstrate that CYC homologues have been independently recruited as determinants of petal identities along the dorsoventral axis in two distant lineages of flowering plants, suggesting a common molecular origin for the mechanisms controlling floral zygomorphy.

Alleles↗

PubMed2006

WdChs1p, a class II chitin synthase, is more responsible than WdChs2p (Class I) for normal yeast reproductive growth in the polymorphic, pathogenic fungus Wangiella (Exophiala) dermatitidis.

The chitin synthase gene WdCHS1 was isolated from a partial genomic DNA library of the pathogenic polymorphic fungus Wangiella dermatitidis. Sequencing showed that WdCHS1 encoded a class II chitin synthase composed of 988 amino acids. Disruption of WdCHS1 produced strains that were hyperpigmented in rich media, grew as yeast at wild-type rates at both 25 and 37 degrees C and were as virulent as the wild type in a mouse model. However, detailed morphological and cytological studies of the wdchs1Delta mutants showed that yeast cells often failed to separate, tended to be enriched with chitin in septal regions and, sometimes, were enlarged with multiple nuclei, had broader mother cell-daughter bud regions and had other cell wall defects seen considerably less often than in the wild type or wdchs2 Delta strains. Disruption of WdCHS1 and WdCHS2 in the same background revealed that WdChs1p had functions synergistic to those of WdChs2p, because mutants devoid of both isozymes produced growth that was very abnormal at 25 degrees C and was not viable at 37 degrees C unless osmotically stabilized. These results suggested that WdChs1p was more responsible than WdChs2p for normal yeast cell reproductive growth because strains with defects in the latter exhibited no morphological abnormalities, whereas those with defects in WdChs1p were frequently impaired in one or more yeast developmental processes.

Animals↗

PubMed2006

Broad-spectrum respiratory tract pathogen identification using resequencing DNA microarrays.

The exponential growth of pathogen nucleic acid sequences available in public domain databases has invited their direct use in pathogen detection, identification, and surveillance strategies. DNA microarray technology has offered the potential for the direct DNA sequence analysis of a broad spectrum of pathogens of interest. However, to achieve the practical attainment of this potential, numerous technical issues, especially nucleic acid amplification, probe specificity, and interpretation strategies of sequence detection, need to be addressed. In this report, we demonstrate an approach that combines the use of a custom-designed Affymetrix resequencing Respiratory Pathogen Microarray (RPM v.1) with methods for microbial nucleic acid enrichment, random nucleic acid amplification, and automated sequence similarity searching for broad-spectrum respiratory pathogen surveillance. Successful proof-of-concept experiments, utilizing clinical samples obtained from patients presenting adenovirus or influenza virus-induced febrile respiratory illness (FRI), demonstrate the ability of this approach for correct species- and strain-level identification with unambiguous statistical interpretation at clinically relevant sensitivity levels. Our results underscore the feasibility of using this approach to expedite the early surveillance of diseases, and provide new information on the incidence of multiple pathogens.

Bacterial Typing Techniques↗

PubMed2006

Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy.

Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy.

Animals↗

PubMed2006

D3 dopamine receptor directly interacts with D1 dopamine receptor in immortalized renal proximal tubule cells.

D3 receptors act synergistically with D1 receptors to inhibit sodium transport in renal proximal tubules; however, the mechanism by which this occurs is not known. Because dopamine receptor subtypes can regulate and interact with each other, we studied the interaction of D3 and D1 receptors in rat renal proximal tubule (RPT) cells. The D3 agonist PD128907 increased the immunoreactive expression of D1 receptors in a concentration- and time-dependent manner; these effects were blocked by the D3 antagonist U99194A. PD128907 also transiently (15 minutes) increased the amount of cell surface membrane D1 receptors. Laser confocal immunofluorescence microscopy showed that D3 receptor and D1 receptor colocalized in RPT cells more distinctly in Wistar-Kyoto rats than in spontaneously hypertensive rats (SHRs). In addition, D3 and D1 receptors could be coimmunoprecipitated, and this interaction was increased after D3 receptor agonist stimulation for 24 hours in Wistar-Kyoto rats but not in SHRs. We propose that the synergistic effects of D3 and D1 receptors may be caused by a D3 receptor-mediated increase in total, as well as cell surface membrane D1 receptor expression, and direct D3 and D1 receptor interaction, both of which are impaired in SHRs.

Animals↗