Biomedical subjects

M Hou

Publications and source records attributed to M Hou.

At least 19 recordsLinked to original sources

PubMed2003

Effects of air on the segregation of particles in a shaken granular bed.

Effects of interstitial air on the motions of a large intruder in a shaken granular bed are studied experimentally as a function of ambient air pressure, particle size of the bed, and the density of the intruder. It is found that the intruder always rises from the granular bed in the absence of air. However, the intruder can acquire both positive and negative buoyancy in the presence of air. Negative buoyancy can be observed only when both the density of the intruder and the particle size of the bed are small enough. This negative buoyancy can be explained by the unusual air pressure distribution found in the bed.

Journal Article↗

PubMed2003

KI-67 AND hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma.

The clinical and histopathological distinction between benign and malignant pheochromocytomas and paragangliomas is difficult, and reliable diagnostic markers are lacking. Here we have evaluated the prognostic value of human telomerase reverse transcriptase (hTERT) gene expression detected by reverse transcription PCR (RT-PCR); telomerase activity (TA) measured by TRAP (telomeric repeat amplification protocol) assay; immunohistochemical staining for Ki-67/MIB-1; and the mRNA expression of matrix metalloproteinase (MMP)-2 and EMMPRIN (extracellular matrix metalloproteinase inducer) analyzed by in situ hybridization in 32 primary pheochromocytomas or abdominal paragangliomas. hTERT was expressed in 7/11 malignant tumors (defined as presence of metastasis and/or extensive local invasion) as compared with in 2/21 benign tumors. All of the benign tumors showed <1% proliferative activity, as measured by Ki-67/MIB-1 staining. In all three patients with malignant tumors who developed metastases and/or invasive local recurrence during follow-up, the tumors were positive for either hTERT expression or Ki-67/MIB-1 immunoreactivity. TA was not a significant discriminator between benign and malignant tumors, and the value of EMMPRIN and MMP-2 as predictive markers was limited. In conclusion, the findings imply that the combined use of Ki-67/MIB-1 and hTERT, in addition to histopathology, provides a highly specific tool to identify benign pheochromocytoma and abdominal paraganglioma cases that are not at risk of developing recurrent or metastatic disease.

Abdominal Neoplasms↗

PubMed2002

Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2.

In migraine and other primary headaches there is a strong vascular component. Besides the trigeminovascular components some of the associated symptoms point to the involvement of brain stem regions. The central limb of the trigeminal vascular pathway is its projection to the trigeminal nucleus caudalis (TNC) and to the C1-C2 levels of the spinal cord. The aim of the present study was to demonstrate the occurrence of some neurotransmitters in these regions in man. In both the TNC and in the Rexed's laminae I and II of the dorsal horns at the C1 and C2 levels there were numerous substance P immunoreactive fibres. Fibres containing calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) were moderately dense in number. Fibres containing vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) were not seen in the TNC or at the C1 and C2 levels of the spinal cord.

Adult↗

PubMed2001

Granular flows through vertical pipes controlled by an electric field.

The flow of granular nickel particles moving down vertical pipes from a hopper in the presence of a local, horizontal ac electric field is studied experimentally. The flow is initiated by opening the bottom outlet of the pipe after the pipe is fully filled with particles from the hopper. The mass of particles flowing out of the pipe is measured as a function of time by an electronic balance. The time dependence of the steady-state flow rate Q, under each fixed voltage V, is obtained. Depending on the magnitude of V, two types of flow behaviors are observed. For low V ( or =V(c)), no interface exists and the whole region between the hopper and the electrodes are densely filled; only one constant flow rate Q(A2) is observed. (The precise meaning of Q(A2) and Q(B) are defined in the text.) The steady-state flow rates Q(A2) and Q(B) measured for each V, are plotted as a function of V. The flow rate Q(A2) is a monotonically decreasing function of V, which can be approximately fitted by a power law, with an exponent of -0.8, while Q(B) is found to be voltage independent. These features result from a competition between the blocking effect of the electric-field region and the gravity-driven pushing effect from the hopper outlet. The local electric field is able to retard the downward movement of a dense column existing above it, but is ineffective in doing so when the column above is dilute in density.

Journal Article↗

PubMed2001

5-HT(1B) and 5-HT(1D) receptors in the human trigeminal ganglion: co-localization with calcitonin gene-related peptide, substance P and nitric oxide synthase.

5-Hydroxytryptamine (5-HT) is implicated in migraine and agonist directed against 5-HT(1B) and 5-HT(1D) receptors are commonly used as effective therapies. The antimigraine mechanisms involve the inhibition of intracranial sensory neuropeptide release. In order to determine which 5-HT(1) receptor subtypes are involved we have by immunocytochemistry examined the distribution of 5-HT(1B) and 5-HT(1D) receptors in the human trigeminal ganglia, and addressed which of them colocalize with calcitonin gene-related peptide (CGRP), substance P (SP) or nitric oxide synthase (NOS). We detected that 5-HT(1D) receptor immunoreactivity (i.r.) was predominantly expressed in medium-sized cells (86% of positive cells, 30-60 microm). About 9% of the 5-HT(1D) receptor i.r. cells were large in size (> 60 microm) and 5% were small in size (< 30 microm). In a similar pattern, 5-HT(1B) receptor i.r. was mainly expressed in medium-sized cells (81% in 30-60 microm, 15% in > 60 microm and 4% in < 30 microm). Double immunostaining was used to determine whether the 5-HT(1B) or 5-HT(1D) receptor immunoreactive cells co-localized with either CGRP, SP or NOS. Thus, 89% of the CGRP i.r. cells expressed 5-HT(1D) receptor i.r. and 65% of the CGRP positive cells were 5-HT(1B) receptor positive. Most of the 5-HT(1D) (95%) and the 5-HT(1B) (94%) receptor i.r. cells showed SP immunostaining and 83% of 5-HT(1D) receptor and 86% of 5-HT(1B) receptor i.r. cells contained NOS. In conclusion, both 5-HT(1B) and 5-HT(1D) receptors are expressed in the human trigeminal ganglion and they are mainly localized in medium-sized cells and they seem to colocalize with CGRP, SP and NOS.

Aged↗

PubMed2001

Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells.

Recent evidence suggests that the Myc and Mad1 proteins are implicated in the regulation of the gene encoding the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. We have analyzed the in vivo interaction between endogenous c-Myc and Mad1 proteins and the hTERT promoter in HL60 cells with the use of the chromatin immunoprecipitation assay. The E-boxes at the hTERT proximal promoter were occupied in vivo by c-Myc in exponentially proliferating HL60 cells but not in cells induced to differentiate by DMSO. In contrast, Mad1 protein was induced and bound to the hTERT promoter in differentiated HL60 cells. Concomitantly, the acetylation of the histones at the promoter was significantly reduced. These data suggest that the reciprocal E-box occupancy by c-Myc and Mad1 is responsible for activation and repression of the hTERT gene in proliferating and differentiated HL60 cells, respectively. Furthermore, the histone deacetylase inhibitor trichostatin A inhibited deacetylation of histones at the hTERT promoter and attenuated the repression of hTERT transcription during HL60 cell differentiation. In addition, trichostatin A treatment activated hTERT transcription in resting human lymphocytes and fibroblasts. Taken together, these results indicate that acetylation/deacetylation of histones is operative in the regulation of hTERT expression.

Acetylation↗

PubMed2001

Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia.

A rat T-cell leukemia model was used to study the safety of germ cell transplantation as a mean of preventing infertility in males undergoing gonadotoxic cancer treatment. Donor germ cells were harvested from the testes of terminally ill leukemic rats and were either used directly or cryopreserved and thawed before transplantation by rete testis microinjection. All rats transplanted with testicular cells from leukemic donors developed signs of terminal rat T-cell leukemia, whereas control animals remained healthy. Cryopreservation of the donor germ cells caused a 3- to 6-day delay in the terminal phase of leukemia. When a known number of leukemic cells were mixed with germ cells and microinjected into the testis, the rate of appearance of terminal leukemia was directly related to the number of transferred leukemic lymphoblasts. As few as 20 leukemic cells were able to cause a cancer relapse resulting in terminal leukemia 21 days after transplantation in three of five transplanted animals. Our results demonstrate that germ cell transplantation with the presently used techniques is not safe enough for clinical use. Improved methods for purging testicular specimens of cancer cells or totally new approaches with transient xenogenetic host models to detect contamination of malignant cells must be developed before this technique can be offered to patients without fear of disease relapse.

Animals↗

PubMed2001

Real-time quantitative telomeric repeat amplification protocol assay for the detection of telomerase activity.

BACKGROUND: Telomerase is a ribonucleoprotein enzyme associated with immortalization and transformation of human cells. The telomeric repeat amplification protocol (TRAP) is widely used for the detection of telomerase activity. The TRAP method, although highly sensitive and specific because it includes PCR amplification, is laborious and does not provide precise quantitative information. METHODS: We developed a real-time quantitative TRAP (RTQ-TRAP) system by combining a real-time PCR technique with the conventional TRAP method. Telomerase activity in human tumor cell lines and in 13 lymphoma samples was measured using the RTQ-TRAP assay, and the results obtained from the samples using the RTQ-TRAP method were compared with the conventional TRAP method. RESULTS: The RTQ-TRAP method was both accurate and reproducible in measuring telomerase activity in a dilution series of protein extracts from HL60 cells. Telomerase activity in 13 lymphoma samples, as determined by the RTQ-TRAP method, was ninefold lower than that measured by the conventional TRAP method. The half-life of telomerase activity in human tumor cells, as determined using RTQ-TRAP, was much shorter than the half-life reported previously. CONCLUSIONS: Our results suggest that the conventional TRAP assay frequently overestimates telomerase activity in tumor samples. The RTQ-TRAP method is thus a useful tool to rapidly and precisely quantify telomerase activity.

Enzyme-Linked Immunosorbent Assay↗

PubMed2001

Telomerase activity in relation to pro- and anti-apoptotic protein expression in high grade non-Hodgkin's lymphomas.

BACKGROUND AND OBJECTIVES: Telomerase activity (TA) is determined by the catalytic unit telomerase reverse transcriptase (hTERT). In vitro studies show that hTERT is downregulated by wild type p53 and TA is upregulated by BCL-2 expression. The aim of this study was to investigate the relationship of TA and mRNA expression of hTERT, telomerase RNA (hTER) and Tankyrase in 31 samples from patients with high-grade non-Hodgkin's lymphoma (HG-NHL). The results were then related to apoptosis and proliferation and the expression of p53 and BCL-2 family member proteins. DESIGN AND METHODS: The telomeric repeat amplification protocol (TRAP) assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to quantify TA, and hTERT, hTER and Tankyrase mRNA expression. Proliferation (Ki67), p53, BCL-2, MCL-1, BAX and BAK protein expression were evaluated by immunohistochemistry. Apoptosis was evaluated by TUNEL staining. RESULTS: TA was detected in 93% of HG-NHL and tended to be higher in p53+ lymphomas. A positive correlation existed between mRNA expression of hTERT, hTER and Tankyrase. hTERT mRNA expression tended to be higher with increasing levels of apoptosis and proliferation, in HG-NHL samples lacking BAX expression and in samples from patients with survival shorter than 3.5 years. hTER mRNA expression was significantly higher in BAX and BAK negative samples. INTERPRETATION AND CONCLUSIONS: Telomerase is activated or upregulated in the majority of HG-NHL. Enhanced TA combined with deregulation of the factors responsible for cell survival and proliferation may contribute to the development and progression of lymphomas. Observation that high hTERT mRNA expression may be related to shorter survival should prompt further investigation of the clinical significance of TA and its components in HG-NHL.

Adult↗

PubMed2001

[The diagnostic value of platelet glycoprotein-specific autoantibody detection in autoimmune thrombocytopenic purpura].

OBJECTIVE: To evaluate the clinical significance of platelet glycoprotein-specific autoantibody detection and platelet-associated IgG (PAIgG) measurement in the differential diagnosis between autoimmune thrombocytopenia and nonimmune thrombocytopenias. METHODS: Anti- GP II b/III a and anti-GP I b/IX autoantibodies were detected by a modified monoclonal antibody immobilization of platelet antigens assay (modified MAIPA), and PAIgG by competitive ELISA. RESULTS: Comparing with the measurement of PAIgG, the GP-specific autoantibody assay was less sensitive but much more specific for the diagnosis of autoimmune thrombocytopenia. CONCLUSION: The platelet GP-specific autoantibody detection is considerably better than PAIgG measurement in discriminating immune from nonimmune thrombocytopenia.

Adolescent↗

PubMed2000

Frequent amplification of the telomerase reverse transcriptase gene in human tumors.

Activation of telomerase is a crucial step during cellular immortalization and malignant transformation of human cells and requires the induction of the catalytic component, human telomerase reverse transcriptase (hTERT), encoded by the hTERT gene. It is poorly understood how the hTERT gene is activated in human cancer cells. In the present study, we examined the hTERT gene copy number in human cancer cell lines and in primary tumor tissues. Amplification of the hTERT gene was observed in 8 of 26 (31%) tumor cell lines and 17 of 58 (30%) primary tumors examined (8 of 21 lung tumors, 3 of 10 cervical tumors, 5 of 19 breast carcinomas, and 1 of 8 neuroblastomas). In addition, 13 of 26 (50%) cell lines and 13 of 58 (22%) primary tumors displayed gain of hTERT gene copies with 3-4 copies/cell. The present findings imply that the hTERT locus may be a frequent target for amplification during tumorigenesis and that this genetic event probably contributes to the dysregulation of telomerase activity occurring in human tumors.

Catalytic Domain↗

PubMed2000

Angiotensin II type 1 receptors stimulate protein synthesis in human cardiac fibroblasts via a Ca2+-sensitive PKC-dependent tyrosine kinase pathway.

The aim of the present study was to investigate the proliferative effects of Ang II in human cardiac fibroblasts. The effects of Ang II in human cardiac fibroblasts on the 3H-thymidine incorporation, the cell number, the 3H-leucine incorporation and the total protein content were measured. The expression of receptor mRNA was performed by reverse transcription-polymerase chain reaction (RT-PCR). Ang II increased 3H-leucine incorporation in a concentration-dependent manner but not 3H-thymidine incorporation in primary cultures of human cardiac fibroblasts. The maximum effect (24 +/- 3% over control) was obtained at a concentration of 10 nM. There were no significant alterations of cell number or total protein content, suggesting that Ang II stimulated protein synthesis but did not induce hypertrophy. The accumulation of 3H-leucine was blocked by the AT1 receptor antagonist candesartan but not by the AT2 receptor antagonist PD123319. By using RT-PCR, both AT1 and AT2 receptors mRNA were found to be expressed in human cardiac fibroblasts. The selective MAPKK inhibitor PD098059, the protein kinase C inhibitor K252a or the phospholipase C inhibitor U73122 did not significantly inhibit Ang II augmented 3H-leucine incorporation. However, this was significantly blocked by the Ca2+-dependent protein kinase C inhibitor GO6976, the non-selective protein kinase inhibitor staurosporine and the tyrosine kinase inhibitor tyrphostin 25. The effects of Ang II were unaffected by the Gi-protein blocker pertussis toxin, indicating a Gi-protein-independent pathway. Ang II was synergistic with insulin but showed no significant increase on 3H-leucine incorporation when combined with PDGF or EGF. In summary, Ang II stimulates protein synthesis through AT1 receptors in human cardiac fibroblasts, but has no hypertrophic or hyperplastic effect. The response is mediated by a MAPKK-independent and Ca2+-sensitive PKC-dependent pathway.

Angiotensin II↗

PubMed2000

Stage-specific inhibition of deoxyribonucleic acid synthesis and induction of apoptosis by antracyclines in cultured rat spermatogenic cells.

A rapid in vitro method has been developed to detect early effects of cytostatic drugs on rat spermatogenesis. The induction of programmed cell death (apoptosis) and changes in DNA synthesis induced by doxorubicin and idarubicin were measured in specific stages of the cycle of seminiferous epithelium including mitotic (stage V) and meiotic (stage VIII-IX) S-phase cells. The model was used to investigate the protective effect of an organic thiophosphate, amifostine, against the toxicity of antracyclines. Premitotic DNA synthesis was found to be more sensitive than premeiotic DNA synthesis to antracyclines. Idarubicin was more toxic than doxorubicin to germ cells in inducing apoptosis and suppressing DNA synthesis. Amifostine had no protective effect against doxorubicin- or idarubicin-induced inhibition of DNA synthesis. In contrast, a significant stimulation of DNA synthesis in premitotic cells by amifostine was found, suggesting that this compound may have a stimulative effect on spermatogenic stem cells. These data show that stage-specific dissection of the seminiferous tubules and their in vitro exposure to predetermined doses of drugs may give us a unique possibility to detect drug action and protection against the cytotoxicity of antineoplastic agents at the cellular level of the spermatogenic cycle.

Animals↗

PubMed2000

Cytokines induce upregulation of vascular P2Y(2) receptors and increased mitogenic responses to UTP and ATP.

P2Y(2) receptors, which mediate contractile and mitogenic effects of extracellular nucleotides in vascular smooth muscle cells (VSMCs), are upregulated in the synthetic phenotype of VSMCs and in the neointima after balloon angioplasty, suggesting a role in the development of atherosclerosis. Because released cytokines in atherosclerotic lesions mediate multiple effects on gene transcription in VSMCs, we speculated that cytokines could be involved in the regulation of P2Y(2) receptor expression. Using a competitive reverse transcription-polymerase chain reaction, we detected that interleukin (IL)-1beta induced a time- and dose-dependent upregulation of P2Y(2) receptor mRNA, which was dramatically enhanced when combined with interferon-gamma or tumor necrosis factor-alpha. Lipopolysaccharide also significantly increased the expression of P2Y(2) receptor mRNA. The upregulation of P2Y(2) receptor mRNA was paralleled at the functional level because IL-1beta significantly increased the UTP-stimulated DNA synthesis and the release of intracellular Ca(2+). Actinomycin D completely blocked the upregulation of P2Y(2) receptor mRNA expression by IL-1beta, indicating de novo mRNA synthesis. There was no cAMP accumulation in the cells stimulated with IL-1beta. The cyclooxygenase inhibitor indomethacin and the protein kinase C inhibitor RO-31-8220 inhibited IL-1beta-induced upregulation of P2Y(2) receptor mRNA expression, whereas rapamycin and PD098059 had no effects. Furthermore, neither P38 mitogen-activated protein kinase inhibitor SB20358 alone nor its combination with PD098059 blocked the effect of IL-1beta on the expression of P2Y(2) receptor mRNA. Our results demonstrate that inflammatory mediators upregulate vascular P2Y(2) receptors at the transcriptional and at the functional level through protein kinase C and cyclooxygenase but not cAMP, extracellular signal-regulated kinases 1 and 2, or P38-dependent pathways. This may result in increased growth-stimulatory or contractile effects of extracellular UTP and ATP, which may be of importance in the development of vascular disease.

Adenosine Triphosphate↗

PubMed2000

Characterization of contractile P2 receptors in human coronary arteries by use of the stable pyrimidines uridine 5'-O-thiodiphosphate and uridine 5'-O-3-thiotriphosphate.

The present study was designed to evaluate the relative contribution of the different contractile P2 receptors in endothelium-denuded human coronary arteries by use of extracellular nucleotides, including the stable pyrimidines uridine 5'-O-3-thiotriphosphate (UTPgammaS) and uridine 5'-O-thiodiphosphate (UDPbetaS). The isometric tension of isolated vessel segments was recorded in vitro, and P2 receptor mRNA expression was examined by reverse transcription-polymerase chain reaction. alphabeta-Methylene-adenosine triphosphate (alphabeta-MeATP) elicited contractions at a low concentration (pEC(50) = 5.2), indicating the presence of contractile P2X receptors. The P2Y responses were analyzed after P2X receptor desensitization with 10 microM alphabeta-MeATP. The stable nucleotides UTPgammaS and adenosine 5'-O-3-thiotriphosphate (ATPgammaS), which are agonists of P2Y(2) or P2Y(4) receptors, were approximately 2 log units more potent than the endogenous UTP and ATP (pEC(50) = 4.6 and 3.8 for UTPgammaS and ATPgammaS). The efficacy of these responses were approximately double that of the P2X agonist alphabeta-MeATP (E(max) = 125% for UTPgammaS, 126% for ATPgammaS, and 68% for alphabeta-MeATP), suggesting a primary role for contractile P2Y(2/4) receptors. The P2Y(2) receptor agonist diadenosine tetraphosphate also stimulated contraction, whereas the selective P2Y(1) agonist adenosine 5'-O-thiodiphosphate and the selective P2Y(6) agonist UDPbetaS had no effect. Reverse transcription-polymerase chain reaction analysis of mRNA from endothelium-denuded human coronary arteries demonstrated strong bands for P2Y(2) and P2X(1), although bands for P2Y(1), P2Y(4), and P2Y(6) receptor mRNA could also be detected. In conclusion, the stable pyrimidines UDPbetaS and UTPgammaS are important tools for P2 receptor subtype characterization in intact tissues with ectonucleotidase activity. Extracellular nucleotides elicit contraction of human coronary arteries primarily by activation of P2Y(2) and P2X receptors, whereas a role for P2Y(1) and P2Y(6) receptors can be excluded. Antagonists of P2Y(2) and P2X receptors may be useful in the treatment of coronary vasospastic disorders.

Adenosine Triphosphate↗

PubMed1999

DNA methylation and expression of p16(INK4A) gene in pulmonary adenocarcinoma and anthracosis in background lung.

The p16 (CDKN2/MTS-1/INK4A) tumor-suppressor gene is frequently inactivated by DNA methylation in lung carcinomas. To clarify whether background anthracosis may play a role in DNA methylation and inactivation of the p16 gene, we examined DNA methylation of the p16-promoter region by methylation-specific polymerase chain reaction, and p16 expression immunohistochemically, and compared the results with the level of background anthracosis which was measured by an original quantitative method. At autopsy, DNA methylation of the p16 gene was observed in 6/19 tumors (32%) from patients who had died of pulmonary adenocarcinoma. The degree of background anthracosis (the effect of extrinsic carcinogenic factors) (mean absorbance value, A = 0.715) of the cases with p16-gene methylation was significantly higher than that without methylation (mean A value = 0.298). p16 expression was inactivated in all tumors with p16-gene methylation. The mean A value of black dust matter deposition in cases with normal expression of p16 (A = 0.151) was significantly lower than cases with abnormal expression of p16 (A = 0.531). These results indicate that the level of background anthracosis is closely associated with inactivation of p16 expression and also DNA methylation of the p16-gene promoter region in pulmonary adenocarcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:609-613, 1999.

Adenocarcinoma↗

PubMed1999

MAPKK-dependent growth factor-induced upregulation of P2Y2 receptors in vascular smooth muscle cells.

The ATP- and UTP-sensitive P2Y2 receptor which mediates both contractile and mitogenic effects has recently been shown to be upregulated in the synthetic phenotype of the vascular smooth muscle cell (VSMC). Using a competitive RT-PCR we demonstrate that the P2Y2 receptor mRNA is increased by fetal calf serum and other growth factors in a MAPKK-dependent way. This was confirmed at the functional level by examining UTP-stimulated release of intracellular Ca2+. Furthermore, the P2Y2 receptor mRNA is positively autoregulated by ATP and the mRNA is rapidly degraded with only 26% remaining after 1 h in the presence of actinomycin D. Our results indicate growth factor regulation and rapid turnover of the P2Y2 receptor mRNA, which may be of importance in atherosclerosis and neointima formation after balloon angioplasty.

Animals↗

PubMed1999

Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure.

We wanted to study the expression of P2-receptors at the mRNA-level in the heart and if it is affected by congestive heart failure (CHF). To quantify the P2 receptor mRNA-expression we used a competitive RT-PCR protocol which is based on an internal RNA standard. The P2 receptor mRNA-expression was quantified in hearts from CHF rats and compared to sham-operated rats. Furthermore, the presence of receptor mRNA was studied in the myocardium from patients with heart failure. In the sham operated rats the G-protein coupled P2Y-receptors were expressed at a higher level than the ligand gated ion-channel receptor (P2X1). Among the P2Y-receptors the P2Y6-receptor was most abundantly expressed (P2Y6 > P2Y1 > P2Y2 = P2Y4 > P2X1). A prominent change was seen for the P2X1- and P2Y2-receptor mRNA levels which were increased 2.7-fold and 4.7-fold respectively in the myocardium from the left ventricle of CHF-rats. In contrast, the P2Y1-, P2Y4- and P2Y6-receptor mRNA levels were not significantly altered in CHF rats. In human myocard the P2X1-, P2Y1-, P2Y2-, P2Y6- and P2Y11-receptors were detected by RT-PCR in both right and left atria and ventricles, while the P2Y4-receptor band was weak or absent. In conclusion, most of the studied P2-receptors were expressed in both rat and human hearts. Furthermore, the P2X1- and P2Y2-receptor mRNA were upregulated in CHF, suggesting a pathophysiological role for these receptors in the development of heart failure.

Adolescent↗