The Experts below are selected from a list of 1491 Experts worldwide ranked by ideXlab platform
Tsutomu Chiba - One of the best experts on this subject based on the ideXlab platform.
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Involvement of β-Adrenergic Receptor Kinase-1 in Homologous Desensitization of Histamine H2 Receptors in Human Gastric Carcinoma Cell Line MKN-45
Digestion, 1996Co-Authors: Hirohisa Nakata, Yoshikazu Kinoshita, Kishi K, Haruhiko Fukuda, Chiharu Kawanami, Yumi Matsushima, Masakyo Asahara, Akihiko Okada, Torn Maekawa, Tsutomu ChibaAbstract:The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H2 receptors which are Homologously desensitized by histamine. In order to clone the cDNA of a receptor kinase specific for H2 receptors, we performed RT-PCR at a low annealing temperature using oligo-DNA primers bearing the conserved sequences of the kinase domain of the G protein-coupled receptor kinase (GRK) family. However, we were able to isolate only cDNAs for beta-adrenergic receptor kinase 1 (beta ARK1) and GRK6. Interestingly, treatment of MKN-45 cells with beta ARK1 antisense phosphorothioate oligo-DNA (PON) resulted in significant loss of Desensitization of H2 receptors by histamine, whereas GRK6 antisense PON had no effect. Thus, beta ARK1 appears to be involved in the Homologous Desensitization of H2 receptors in MKN-45 cells.
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Homologous Desensitization of histamine h2 receptors in the human gastric carcinoma cell line mkn 45
American Journal of Physiology-gastrointestinal and Liver Physiology, 1993Co-Authors: Noriyuki Arima, Yoshikazu Kinoshita, A Nakamura, Y Yamashita, Tsutomu ChibaAbstract:The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H2 receptors, which are linked to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production. Pretreatment of MKN-45 cells with histamine elicited a rapid and dose-dependent inhibition of cAMP production in response to subsequent administration of histamine, whereas pretreatment with prostaglandin E2 (PGE2) or forskolin, both of which stimulate cAMP formation in these cells, had no effect on the histamine-induced cAMP production. Neither NaF- nor forskolin-induced cAMP production was affected by histamine pretreatment. Scatchard analysis of data obtained for [3H]-tiotidine binding showed that histamine pretreatment affected neither the number of histamine H2 receptors nor the binding affinity of the ligand for the receptors. Finally, histamine pretreatment had no effect on cAMP response to subsequent addition of PGE2, which was reduced by PGE2 pretreatment. These results suggest that histamine induces Homologous Desensitization of H2 receptors on MKN-45 cells by a mechanism that does not involve stimulation of cAMP production.
Yoshikazu Kinoshita - One of the best experts on this subject based on the ideXlab platform.
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Involvement of β-Adrenergic Receptor Kinase-1 in Homologous Desensitization of Histamine H2 Receptors in Human Gastric Carcinoma Cell Line MKN-45
Digestion, 1996Co-Authors: Hirohisa Nakata, Yoshikazu Kinoshita, Kishi K, Haruhiko Fukuda, Chiharu Kawanami, Yumi Matsushima, Masakyo Asahara, Akihiko Okada, Torn Maekawa, Tsutomu ChibaAbstract:The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H2 receptors which are Homologously desensitized by histamine. In order to clone the cDNA of a receptor kinase specific for H2 receptors, we performed RT-PCR at a low annealing temperature using oligo-DNA primers bearing the conserved sequences of the kinase domain of the G protein-coupled receptor kinase (GRK) family. However, we were able to isolate only cDNAs for beta-adrenergic receptor kinase 1 (beta ARK1) and GRK6. Interestingly, treatment of MKN-45 cells with beta ARK1 antisense phosphorothioate oligo-DNA (PON) resulted in significant loss of Desensitization of H2 receptors by histamine, whereas GRK6 antisense PON had no effect. Thus, beta ARK1 appears to be involved in the Homologous Desensitization of H2 receptors in MKN-45 cells.
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Homologous Desensitization of histamine h2 receptors in the human gastric carcinoma cell line mkn 45
American Journal of Physiology-gastrointestinal and Liver Physiology, 1993Co-Authors: Noriyuki Arima, Yoshikazu Kinoshita, A Nakamura, Y Yamashita, Tsutomu ChibaAbstract:The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H2 receptors, which are linked to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production. Pretreatment of MKN-45 cells with histamine elicited a rapid and dose-dependent inhibition of cAMP production in response to subsequent administration of histamine, whereas pretreatment with prostaglandin E2 (PGE2) or forskolin, both of which stimulate cAMP formation in these cells, had no effect on the histamine-induced cAMP production. Neither NaF- nor forskolin-induced cAMP production was affected by histamine pretreatment. Scatchard analysis of data obtained for [3H]-tiotidine binding showed that histamine pretreatment affected neither the number of histamine H2 receptors nor the binding affinity of the ligand for the receptors. Finally, histamine pretreatment had no effect on cAMP response to subsequent addition of PGE2, which was reduced by PGE2 pretreatment. These results suggest that histamine induces Homologous Desensitization of H2 receptors on MKN-45 cells by a mechanism that does not involve stimulation of cAMP production.
Gang Pei - One of the best experts on this subject based on the ideXlab platform.
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differential efficacies of κ agonists to induce Homologous Desensitization of human κ opioid receptor
Neuroscience Letters, 1998Co-Authors: Kun Ling, Gang PeiAbstract:The efficacies of different K agonists to activate K opioid receptor (kappaOR) and to induce acute Homologous Desensitization of kappaOR-mediated extracellular acidification response (ECAR) have been investigated using microphysiometry in Chinese hamster ovary (CHO) cells stably expressing kappaOR. Although efficacy of dynorphin A (DA) to stimulate kappaOR-mediated ECAR was comparable to that of U69593, DA displayed a significant higher efficacy to induce Desensitization of kappaOR. Moreover, the half life for the recovery of kappaOR responsiveness after DA prechallenge was four times longer than those observed after U69593 or etorphine pretreatment. In contrast, the efficacy of DA to stimulate and desensitize mu opioid receptors (muOR) stably expressed in CHO cells were comparable to those of other mu agonists.
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endogenous opioid receptor like receptor in human neuroblastoma sk n sh cells activation of inhibitory g protein and Homologous Desensitization
Neuroreport, 1997Co-Authors: Zhijie Cheng, Guohuang Fan, Jian Zhao, Zhe Zhang, Lizhen Jiang, Ye Zhu, Gang PeiAbstract:Endogenous expression of opioid receptor-like receptor (ORL1), in human neuroblastoma SK-N-SH cells was demonstrated by binding with nociceptin/ orphanin FQ (N/OFQ). Scatchard analysis of [3H]N/ OFQ saturation binding data gave Kd = 1.3 +/- 0.1 nM and Bmax = 1.58 +/- 2.5 fmol/mg protein. N/OFQ stimulation increased [35S]GTP gamma S binding to cell membranes and attenuated forskolin-induced cAMP accumulation in a concentration-dependent manner. The effects of N/OFQ were eliminated by the pretreatment of pertussis toxin (PTX) but not by the antagonists of opioid receptors, revealing mediation of N/OFQ signal transduction by ORL1 receptor and PTX sensitive G protein(s). The ability of N/OFQ to inhibit cAMP production was greatly reduced after prechallenging with N/OFQ, indicating that ORL1 undergoes Homologous Desensitization in neuronal cells.
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delta opioid receptor in neuronal cells undergoes acute and Homologous Desensitization
Biochemical and Biophysical Research Communications, 1996Co-Authors: Yingchun Cai, Yi Zhang, Gang PeiAbstract:Using delta opioid receptor as a model system, acute Desensitization of neuronal opioid receptor was studied in detail in neuroblastoma x glioma NG108-15 cells and primarily-cultured mouse cortical cells. The opioid Desensitization could occur in as short as 3 minutes of agonist treatment and the half-life of the desensitized state was about 90 minutes. This acute opioid Desensitization was Homologous in nature in both neuronal cells. The acute Desensitization was almost abolished by treatment of the neuronal cells with staurosporine, a nonspecific protein kinase inhibitor. Treatment with the protein kinase C-selective inhibitor, calphostin C, however, caused partial block. In conclusion, neuronal opioid receptor undergoes acute, agonist-dependent, and Homologous Desensitization, during which protein kinases appear to play an important role.
Kazuo Chihara - One of the best experts on this subject based on the ideXlab platform.
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interaction of parathyroid hormone related peptide responsive dual signal transduction systems in osteoblastic osteosarcoma cells role in pthrp induced Homologous Desensitization
Journal of Bone and Mineral Research, 2009Co-Authors: Toshitsugu Sugimoto, Junichi Kano, Kazuto Ikeda, Masaaki Fukase, Kazuo ChiharaAbstract:In Osteoblastic Umr-106 Cells, 10−7 M human (h) PTH-related peptide (PTHrP)-(1–34) significantly induced the formation of total inositol phosphates to the same degree as 10−7 M hPTH-(1–34), confirming that in addition to cAMP-dependent protein kinase (PKA), PTHrP possesses another signal transduction system, calcium/protein kinase C (Ca/PKC). Experiments were therefore performed to characterize the cross talk of these dual-signal transduction systems and its participation in the PTHrP-induced Homologous Desensitization of cAMP and cytosolic calcium (Cai) response in osteoblasts. Preincubation with 10−7 M hPTHrP-(1–34) caused Homologous Desensitization, resulting in a remarkable decrease in cAMP accumulation in response to further exposure to PTHrP. This effect was significant after 2 h pretreatment and reached a maximum at 6 h. Pretreatment with the PKC-activating phorbol ester phorbol 12-myristate-13-acetate (PMA, 10−6 M) for 30 minutes and 6 h caused a significant increase and decrease in cAMP responsiveness to PTHrP, respectively. Pretreatment with calcium ionophores (A23187 or ionomycin, 10−6 M), not for 30 minutes but for 6 h, caused a significant decrease in cAMP responsiveness to PTHrP. H-7 (an inhibitor of PKC, 50 μM) significantly blocked not only PMA- but also PTHrP-induced Desensitization of the cAMP response. PTHrP caused the complete Homologous Desensitization of an increase in Cai within 30 minutes. Pretreatment with dibutyryl-cAMP (10−4 M) for 30 minutes caused significant inhibition of the PTHrP-induced increase in Cai, and pretreatment with Sp-cAMPS (10−4 M), a direct activator of PKA, for 30 minutes completely blocked the PTHrP-induced increase in Cai. Rp-cAMPS (10−4 M), an antagonist in the activation of PKA, slightly but significantly antagonized the PTHrP-induced Homologous Desensitization of the Cai response. The present study demonstrated the existence of cross-talk in PTHrP-responsive dual signal transduction systems and its participation in PTHrP-induced Homologous Desensitization.
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cross talk of parathyroid hormone responsive dual signal transduction systems in osteoblastic osteosarcoma cells its role in pth induced Homologous Desensitization of intracellular calcium response
Journal of Cellular Physiology, 1994Co-Authors: Toshitsugu Sugimoto, Junichi Kano, Kazuto Ikeda, Masaaki Fukase, Toru Yamaguchi, Kazuo ChiharaAbstract:The present study was designed to characterize the cross-talk of parathyroid hormone (PTH)-responsive dual signal transduction systems (cAMP-dependent protein kinase (PKA) and calcium/protein kinase C [PKC]) and its participation in PTH-induced Homologous Desensitization of intracellular calcium ([Ca2+]i) in osteoblastic UMR-106 cells. Although our recent study revealed that prolonged (more than 2 h) pretreatment with PKC-activating phorbol ester, phorbol 12-myristate 13-acetate (PMA) significantly decreased the PTH-stimulated cAMP production, pretreatment with PMA (10(-7) and 10(-6) M) but not 10(-6) M 4 alpha-phorbol 12,13-didecanoate (PDD), incapable of activating PKC for 30 min significantly augmented 10(-7) M hPTH-(1-34)-stimulated cAMP production. H-7 (50 microM), a PKC inhibitor, significantly antagonized this PMA-induced effect. Pretreatment with 10(-6) M PMA for 30 min did not affect PTH receptor binding but significantly augmented a cAMP responsiveness to 10(-5) M forskolin and 1 microgram/ml cholera toxin. Pertussis toxin (0.5 microgram/ml) did not affect the PMA-induced augmentation of the PTH-stimulated cAMP production. PTH caused a complete Homologous Desensitization of [Ca2+]i response within 30 min. Pretreatment with 10(-4) M dibutyryl cAMP for 30 min and 6 h significantly reduced and completely blocked the PTH-induced increase in [Ca2+]i, respectively. Pretreatment with 10(-4) M Sp-cAMPs, a direct PKA activator, for 30 min completely blocked the PTH-induced increase in [Ca2+]i. Rp-cAMPS (10(-4) M), an antagonist of PKA, slightly but significantly antagonized the PTH-induced Homologous Desensitization of [Ca2+]i response. The present study indicates that the time of exposure to PKC activation is a critical determinant in modulating the cAMP system, while PKA activation counterregulatorily acts on the [Ca2+]i system, and that PKA activation is linked to the PTH-induced Homologous Desensitization of [Ca2+]i response.
Toshitsugu Sugimoto - One of the best experts on this subject based on the ideXlab platform.
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interaction of parathyroid hormone related peptide responsive dual signal transduction systems in osteoblastic osteosarcoma cells role in pthrp induced Homologous Desensitization
Journal of Bone and Mineral Research, 2009Co-Authors: Toshitsugu Sugimoto, Junichi Kano, Kazuto Ikeda, Masaaki Fukase, Kazuo ChiharaAbstract:In Osteoblastic Umr-106 Cells, 10−7 M human (h) PTH-related peptide (PTHrP)-(1–34) significantly induced the formation of total inositol phosphates to the same degree as 10−7 M hPTH-(1–34), confirming that in addition to cAMP-dependent protein kinase (PKA), PTHrP possesses another signal transduction system, calcium/protein kinase C (Ca/PKC). Experiments were therefore performed to characterize the cross talk of these dual-signal transduction systems and its participation in the PTHrP-induced Homologous Desensitization of cAMP and cytosolic calcium (Cai) response in osteoblasts. Preincubation with 10−7 M hPTHrP-(1–34) caused Homologous Desensitization, resulting in a remarkable decrease in cAMP accumulation in response to further exposure to PTHrP. This effect was significant after 2 h pretreatment and reached a maximum at 6 h. Pretreatment with the PKC-activating phorbol ester phorbol 12-myristate-13-acetate (PMA, 10−6 M) for 30 minutes and 6 h caused a significant increase and decrease in cAMP responsiveness to PTHrP, respectively. Pretreatment with calcium ionophores (A23187 or ionomycin, 10−6 M), not for 30 minutes but for 6 h, caused a significant decrease in cAMP responsiveness to PTHrP. H-7 (an inhibitor of PKC, 50 μM) significantly blocked not only PMA- but also PTHrP-induced Desensitization of the cAMP response. PTHrP caused the complete Homologous Desensitization of an increase in Cai within 30 minutes. Pretreatment with dibutyryl-cAMP (10−4 M) for 30 minutes caused significant inhibition of the PTHrP-induced increase in Cai, and pretreatment with Sp-cAMPS (10−4 M), a direct activator of PKA, for 30 minutes completely blocked the PTHrP-induced increase in Cai. Rp-cAMPS (10−4 M), an antagonist in the activation of PKA, slightly but significantly antagonized the PTHrP-induced Homologous Desensitization of the Cai response. The present study demonstrated the existence of cross-talk in PTHrP-responsive dual signal transduction systems and its participation in PTHrP-induced Homologous Desensitization.
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cross talk of parathyroid hormone responsive dual signal transduction systems in osteoblastic osteosarcoma cells its role in pth induced Homologous Desensitization of intracellular calcium response
Journal of Cellular Physiology, 1994Co-Authors: Toshitsugu Sugimoto, Junichi Kano, Kazuto Ikeda, Masaaki Fukase, Toru Yamaguchi, Kazuo ChiharaAbstract:The present study was designed to characterize the cross-talk of parathyroid hormone (PTH)-responsive dual signal transduction systems (cAMP-dependent protein kinase (PKA) and calcium/protein kinase C [PKC]) and its participation in PTH-induced Homologous Desensitization of intracellular calcium ([Ca2+]i) in osteoblastic UMR-106 cells. Although our recent study revealed that prolonged (more than 2 h) pretreatment with PKC-activating phorbol ester, phorbol 12-myristate 13-acetate (PMA) significantly decreased the PTH-stimulated cAMP production, pretreatment with PMA (10(-7) and 10(-6) M) but not 10(-6) M 4 alpha-phorbol 12,13-didecanoate (PDD), incapable of activating PKC for 30 min significantly augmented 10(-7) M hPTH-(1-34)-stimulated cAMP production. H-7 (50 microM), a PKC inhibitor, significantly antagonized this PMA-induced effect. Pretreatment with 10(-6) M PMA for 30 min did not affect PTH receptor binding but significantly augmented a cAMP responsiveness to 10(-5) M forskolin and 1 microgram/ml cholera toxin. Pertussis toxin (0.5 microgram/ml) did not affect the PMA-induced augmentation of the PTH-stimulated cAMP production. PTH caused a complete Homologous Desensitization of [Ca2+]i response within 30 min. Pretreatment with 10(-4) M dibutyryl cAMP for 30 min and 6 h significantly reduced and completely blocked the PTH-induced increase in [Ca2+]i, respectively. Pretreatment with 10(-4) M Sp-cAMPs, a direct PKA activator, for 30 min completely blocked the PTH-induced increase in [Ca2+]i. Rp-cAMPS (10(-4) M), an antagonist of PKA, slightly but significantly antagonized the PTH-induced Homologous Desensitization of [Ca2+]i response. The present study indicates that the time of exposure to PKC activation is a critical determinant in modulating the cAMP system, while PKA activation counterregulatorily acts on the [Ca2+]i system, and that PKA activation is linked to the PTH-induced Homologous Desensitization of [Ca2+]i response.
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protein kinase c is involved in pth induced Homologous Desensitization by directly affecting pth receptor in the osteoblastic osteosarcoma cells
Endocrinology, 1991Co-Authors: Kazuto Ikeda, Toshitsugu Sugimoto, Masaaki Fukase, Takuo FujitaAbstract:We have investigated mechanisms of PTH-induced Homologous Desensitization reflected in the refractoriness of cAMP response to the second exposure to PTH in the clonal rat osteosarcoma cell line, UMR-106. Preincubation with 10(-7) M rat (r) PTH-(1-34) for 6 h caused the Desensitization, resulting in a 65% decrease in cAMP accumulation in response to further exposure to rPTH. This Desensitization was apparent at 10(-10) M rPTH and maximal at 10(-7) M rPTH. UMR-106 cells treated with protein kinase C (PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 10(-6) M) for 6 h also induced Desensitization manifested by a loss of rPTH-stimulated cAMP accumulation to 50% of that in the control cells. On the other hand, 4 alpha-phorbol 12,13-didecanoate, incapable of activating PK-C, failed to induce Desensitization. Fifty micromolar H-7 (PK-C inhibitor) significantly blocked both rPTH- and PMA-induced Desensitization. Thus, PK-C seemed to play a major role in rPTH-induced Desensitization. Pretreatment with neither rPTH nor PMA changed the cAMP responsiveness to 10 micrograms/ml cholera toxin or 100 microM forskolin. Islet activating protein failed to influence the Desensitization in this cell line. PTH receptor binding, assessed by using 125I-labeled [Nle8,Nle18,Tyr34]PTH-(1-34) as a radioligand, was decreased along with PTH receptor numbers by pretreatment with rPTH or PMA. These data indicate that rPTH-induced Homologous Desensitization occurs at least in part through the activation of PK-C and that PK-C directly affects PTH receptor in UMR-106 cells.