Receptor Antagonist D2

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C. Kohler - One of the best experts on this subject based on the ideXlab platform.

  • Effects of dopamine D-1 and D-2 Receptors on intraocular pressure in conscious rabbits
    Journal of Neural Transmission, 1997
    Co-Authors: C. Prünte, I. Nuttli, R. Markstein, C. Kohler
    Abstract:

    This investigation was designed as a randomized, placebocontrolled, double-masked, crossover study in NZW rabbits with normal intraocular pressure (IOP) to investigate dopaminergic effects on IOP. SKF 38393, a selective D1-Receptor agonist, increased, and SDZ PSD-958, a selective D1-Receptor Antagonist, decreased IOP, respectively. The selective D2-Receptor agonist quinpirole decreased IOP, whereas the selective D2 Receptor Antagonist metoclopramide had no significant effect. Combinations of quinpirole with SDZ PSD-958 decreased IOP in an additive manner. SDZ GLC-756, a mixed D1-Receptor Antagonist/D2-Receptor agonist, decreased IOP in a dose-dependent manner with a maximum effect greater than the maximum effects produced either by the D1-Receptor Antagonist SDZ PSD-958 and the D2-Receptor agonist quinpirole. The effect of SDZ GLC-756 could only be partially blocked by the selective D2-Receptor Antagonist metoclopramide suggesting that both D1-Receptor blockade and D2-Receptor stimulation participate in its IOP-lowering effect. Tonography suggests that SDZ GLC-756 has no significant effect on outflow facility. Furthermore, the results suggest that both D1 and D2 Receptors each play an independent role in the regulation of IOP in rabbits. Thus, simultaneous blockade of D1 Receptors and stimulation of D2 Receptors may provide a new pharmacological approach for the treatment of ocular hypertension frequently associated with glaucoma.

C. Prünte - One of the best experts on this subject based on the ideXlab platform.

  • Effects of dopamine D-1 and D-2 Receptors on intraocular pressure in conscious rabbits
    Journal of Neural Transmission, 1997
    Co-Authors: C. Prünte, I. Nuttli, R. Markstein, C. Kohler
    Abstract:

    This investigation was designed as a randomized, placebocontrolled, double-masked, crossover study in NZW rabbits with normal intraocular pressure (IOP) to investigate dopaminergic effects on IOP. SKF 38393, a selective D1-Receptor agonist, increased, and SDZ PSD-958, a selective D1-Receptor Antagonist, decreased IOP, respectively. The selective D2-Receptor agonist quinpirole decreased IOP, whereas the selective D2 Receptor Antagonist metoclopramide had no significant effect. Combinations of quinpirole with SDZ PSD-958 decreased IOP in an additive manner. SDZ GLC-756, a mixed D1-Receptor Antagonist/D2-Receptor agonist, decreased IOP in a dose-dependent manner with a maximum effect greater than the maximum effects produced either by the D1-Receptor Antagonist SDZ PSD-958 and the D2-Receptor agonist quinpirole. The effect of SDZ GLC-756 could only be partially blocked by the selective D2-Receptor Antagonist metoclopramide suggesting that both D1-Receptor blockade and D2-Receptor stimulation participate in its IOP-lowering effect. Tonography suggests that SDZ GLC-756 has no significant effect on outflow facility. Furthermore, the results suggest that both D1 and D2 Receptors each play an independent role in the regulation of IOP in rabbits. Thus, simultaneous blockade of D1 Receptors and stimulation of D2 Receptors may provide a new pharmacological approach for the treatment of ocular hypertension frequently associated with glaucoma.

I. Nuttli - One of the best experts on this subject based on the ideXlab platform.

  • Effects of dopamine D-1 and D-2 Receptors on intraocular pressure in conscious rabbits
    Journal of Neural Transmission, 1997
    Co-Authors: C. Prünte, I. Nuttli, R. Markstein, C. Kohler
    Abstract:

    This investigation was designed as a randomized, placebocontrolled, double-masked, crossover study in NZW rabbits with normal intraocular pressure (IOP) to investigate dopaminergic effects on IOP. SKF 38393, a selective D1-Receptor agonist, increased, and SDZ PSD-958, a selective D1-Receptor Antagonist, decreased IOP, respectively. The selective D2-Receptor agonist quinpirole decreased IOP, whereas the selective D2 Receptor Antagonist metoclopramide had no significant effect. Combinations of quinpirole with SDZ PSD-958 decreased IOP in an additive manner. SDZ GLC-756, a mixed D1-Receptor Antagonist/D2-Receptor agonist, decreased IOP in a dose-dependent manner with a maximum effect greater than the maximum effects produced either by the D1-Receptor Antagonist SDZ PSD-958 and the D2-Receptor agonist quinpirole. The effect of SDZ GLC-756 could only be partially blocked by the selective D2-Receptor Antagonist metoclopramide suggesting that both D1-Receptor blockade and D2-Receptor stimulation participate in its IOP-lowering effect. Tonography suggests that SDZ GLC-756 has no significant effect on outflow facility. Furthermore, the results suggest that both D1 and D2 Receptors each play an independent role in the regulation of IOP in rabbits. Thus, simultaneous blockade of D1 Receptors and stimulation of D2 Receptors may provide a new pharmacological approach for the treatment of ocular hypertension frequently associated with glaucoma.

R. Markstein - One of the best experts on this subject based on the ideXlab platform.

  • Effects of dopamine D-1 and D-2 Receptors on intraocular pressure in conscious rabbits
    Journal of Neural Transmission, 1997
    Co-Authors: C. Prünte, I. Nuttli, R. Markstein, C. Kohler
    Abstract:

    This investigation was designed as a randomized, placebocontrolled, double-masked, crossover study in NZW rabbits with normal intraocular pressure (IOP) to investigate dopaminergic effects on IOP. SKF 38393, a selective D1-Receptor agonist, increased, and SDZ PSD-958, a selective D1-Receptor Antagonist, decreased IOP, respectively. The selective D2-Receptor agonist quinpirole decreased IOP, whereas the selective D2 Receptor Antagonist metoclopramide had no significant effect. Combinations of quinpirole with SDZ PSD-958 decreased IOP in an additive manner. SDZ GLC-756, a mixed D1-Receptor Antagonist/D2-Receptor agonist, decreased IOP in a dose-dependent manner with a maximum effect greater than the maximum effects produced either by the D1-Receptor Antagonist SDZ PSD-958 and the D2-Receptor agonist quinpirole. The effect of SDZ GLC-756 could only be partially blocked by the selective D2-Receptor Antagonist metoclopramide suggesting that both D1-Receptor blockade and D2-Receptor stimulation participate in its IOP-lowering effect. Tonography suggests that SDZ GLC-756 has no significant effect on outflow facility. Furthermore, the results suggest that both D1 and D2 Receptors each play an independent role in the regulation of IOP in rabbits. Thus, simultaneous blockade of D1 Receptors and stimulation of D2 Receptors may provide a new pharmacological approach for the treatment of ocular hypertension frequently associated with glaucoma.

Andrea Todisco - One of the best experts on this subject based on the ideXlab platform.

  • Molecular mechanisms for the growth factor action of gastrin.
    Journal of Gastroenterology, 2000
    Co-Authors: Andrea Todisco
    Abstract:

    Todisco, Andrea, Yoshiaki Takeuchi, Andrej Urumov, Junko Yamada, Vinzenz M. Stepan, and Tadataka Yamada. Molecular mechanisms for the growth factor action of gastrin. Am. J. Physiol. 273 (Gastrointest. Liver Physiol. 36): G891–G898, 1997.—We have previously observed that gastrin has a cholecystokinin B (CCK-B) Receptor-mediated growth-promoting effect on the AR42J rat pancreatic acinar cell line and that this effect is paralleled by induction of expression of the early response gene c-fos. We undertook these experiments to elucidate the mechanism for induction of c-fos and the linkage of this action to the trophic effects of gastrin. Gastrin (0.1–10 nM) dose dependently induced luciferase activity in AR42J cells transfected with a construct consisting of a luciferase reporter gene coupled to the serum response element (SRE) of the c-fos promoter. This effect was blocked by the specific CCK-B Receptor Antagonist D2 but not by the specific CCK-A Receptor Antagonist L-364,718 or by pertussis toxin, indicating that gastrin targets the SRE via specific CCK-B Receptors through a mechanism independent of Gi. Inhibition of protein kinase C (PKC) either by prolonged (24 h) exposure of the cells to the phorbol ester 12-Otetradecanoylphorbol 13-acetate (100 nM) or by incubation with the selective inhibitor GF-109203X (3.5 μM) resulted in an 80% reduction in luciferase activity. Similar results were observed in the presence of the specific extracellular signalregulated kinase (ERK) kinase (MEK) inhibitor PD-98059 (50 μM). We measured ERK2 activity in AR42J cells via in-gel kinase assays and observed that gastrin (1 pM-100 nM) induced ERK2 enzyme activity in a dose-dependent manner. Addition of GF-109203X and PD-98059, either alone or in combination, produced, respectively, partial and total inhibition of gastrin-induced ERK2 activity. Gastrin induction of ERK2 activity also resulted in a threefold increase in the transcriptional activity of Elk-1, a factor known to bind to the c-fos SRE and to be phosphorylated and activated by ERK2. PD-98059 blocked the growth-promoting effect of gastrin on the AR42J cells, demonstrating that this effect depends on activation of MEK. Our data lead us to conclude that the trophic actions of gastrin are mediated by ERK2-induced c-fos gene expression via PKC-dependent and -independent pathways.