The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform
Naohiko Takahata - One of the best experts on this subject based on the ideXlab platform.
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Potential antidepressant properties of Forskolin and a novel water-soluble Forskolin (NKH477) in the forced swimming test
Life sciences, 1997Co-Authors: Hideo Maeda, Hiroki Ozawa, Toshikazu Saito, Tsuyoshi Irie, Naohiko TakahataAbstract:Abstract The mechanisms of the antidepressant activity of Forskolin and a novel water soluble Forskolin analog (NKH477) were studied using the forced swimming method in rats. Forskolin (0.01–0.1 mg/kg) and NKH477 (0.01–0.1 mg/kg) dose-dependently decreased ratings of immobility, with effects similar to those of amitriptyline treatment. The maximum effects of Forskolin and NKH477 were observed at 0.01 mg/kg dose which is 150 more times potent than that (15 mg/kg) of amitriptyline. At a high dose (1.0 mg/kg) of Forskolin and NKH477, the duration of immobility was returned to control levels. Forskolin and NKH477 did not influence the spontaneous locomotor activity at intraperitoneal injection doses from 0.01 to 1 mg/kg. Furthermore chronic administration with NKH477 at oral dose from 0.5 to 1.5 mg/kg significantly decreases the duration of immobility. These data indicate that both Forskolin and NKH477 have strong antidepressive potency, consistent with the hypothesis that elevation of the cAMP cascade system may have an important role in antidepressive effects.
Goldstein I - One of the best experts on this subject based on the ideXlab platform.
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G-protein-coupled receptor agonists augment adenylyl cyclase activity induced by Forskolin in human corpus cavernosum smooth muscle cells.
Receptors & signal transduction, 1997Co-Authors: Abdul Traish, Gallant C, Goldstein IAbstract:The goal of this study was to investigate the synergistic effects between G-protein-coupled receptor agonists and Forskolin-induced activation of adenylyl cyclases, in cultured human corpus cavernosum smooth-muscle cells. Treatment of human corpus cavernosum smooth-muscle cells with Forskolin (0.1-10 microM) produced an increase in cAMP synthesis in a concentration-dependent manner. Forskolin-induced adenylyl cyclase activity was markedly augmented by prostaglandin E1 (PGE1) and its metabolite, PGE0, isoproterenol, carbachol, and phenylephrine. Augmentation of Forskolin-induced cAMP by PGE1, and PGE0 is probably mediated by prostaglandin E receptors (EP). Enhancement of Forskolin-induced cAMP synthesis by isoproterenol is mediated by beta-adrenergic receptors (beta-AR), since this activity was inhibited by propranolol. Stimulation of Forskolin-induced cAMP synthesis by carbachol is attributed to activation of muscarinic acetylcholine receptors (mAChR), as demonstrated by inhibition with atropine. The augmentation of Forskolin-induced cAMP synthesis by phenylephrine, an alpha1-adrenergic receptor (AR) agonist, however, was unexpected and cannot be attributed to increased intracellular Ca2+, since treatment of cells with either the Ca2+ ionophore, A23187, or 80 mM KCl did not affect Forskolin-induced cAMP synthesis. Stimulation of Forskolin-induced cAMP synthesis by phenylephrine is explained by its binding to beta-AR and activation of Gs protein, since this augmentation was inhibited by the beta-AR antagonist, propranolol. This observation was further supported by physiological studies in organ bath chambers, in which Forskolin-induced relaxation of precontracted corpus cavernosum strips was enhanced by phenylephrine. These studies suggest that synergism between agonist-induced cAMP synthesis and Forskolin is attributed to increased conformational stabilization of activated adenylyl cyclase catalytic domains by Forskolin and the Gs(alpha)-subunit of activated Gs proteins.
Lir-wan Fan - One of the best experts on this subject based on the ideXlab platform.
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Effects of CAMP elevating agents on carbachol-induced phosphoinositide hydrolysis and calcium mobilization in cultured canine tracheal smooth muscle cells
Cell calcium, 1996Co-Authors: Chuen-mao Yang, Ming-che Hsu, Hui-liang Tsao, Chi-tso Chiu, Ong R, Jen-tsung Hsieh, Lir-wan FanAbstract:Abstract The effects of increases in intracellular adenosine 3′,5′-cyclic monophosphate (CAMP) on carbachol-induced generation of inositol phosphates (IPs) and increases in intracellular Ca 2+ ([Ca 2+ ] i ) were investigated in canine cultured tracheal smooth muscle cells (TSMCs). The CAMP elevating agents, cholera toxin (CTX) and Forskolin, induced concentration- and time-dependent CAMP formation with half-maximal effects (-IogEC 50 ) at concentrations of 7.6 ± 1.3 g/ml and 4.8 ± 0.9 M, respectively. Forskolin caused a concentration-dependent inhibition of carbachol-induced increase in [Ca 2+ ] i with half-maximal inhibition (-IogEC 50 at 5.2 ± 0.7 M. Pretreatment of TSMCs with either CTX (10 μ/ml, 4 h), Forskolin (10–100 μM, 30 min), or dibutyryl CAMP (1 mM, 30 min) inhibited carbachol-stimulated Ca 2+ mobilization and IPs accumulation. The inhibitory effects of these agents produced both depression of the maximal response and a shift to the right of the concentration-response curve of carbachol without changing the EC 50 values. After treatment with Forskolin for 24 h, carbachol-induced IPs accumulation and Ca 2+ mobilization were close to those of control group. SQ-22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, 10 μM], an inhibitor of adenylate cyclase, and HA-1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride, 50 μM], an inhibitor of CAMP-dependent protein kinase (PKA), attenuated the ability of Forskolin to inhibit carbachol-induced IPs accumulation. Moreover, the inactive analogue of Forskolin, 1,9-dideoxy Forskolin, did not inhibit these responses evoked by carbachol, suggesting that activation of CAMP/PKA was involved in these inhibitory effects of Forskolin. The K D and B max values of the muscarinic receptor (mAChR) for [ 3 H]-N-methyl scopolamine binding were not significantly changed by Forskolin treatment for 30 min and 24 h, suggesting that the inhibitory effect of Forskolin is distal to the mAChR. The locus of this inhibition was further investigated by examining the effect of Forskolin treatment on AIF 4 -stimulated IPs accumulation in canine TSMCs. The AIF 4 -induced response was inhibited by Forskolin, supporting the notion that G protein(s) are directly activated by AIF4 and uncoupled to phospholipase C by Forskolin treatment. We conclude that CAMP elevating agents inhibit carbachol-stimulated generation of IPs and Ca 2+ mobilization in canine cultured TSMCs. Since generation of IPs and increases in [Ca 2+ ]; are very early events in the activation of mAChRs, attenuation of these events by cAMP elevating agents might well contribute to the inhibitory effect of CAMP on tracheal smooth muscle function.
Hideo Maeda - One of the best experts on this subject based on the ideXlab platform.
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Potential antidepressant properties of Forskolin and a novel water-soluble Forskolin (NKH477) in the forced swimming test
Life sciences, 1997Co-Authors: Hideo Maeda, Hiroki Ozawa, Toshikazu Saito, Tsuyoshi Irie, Naohiko TakahataAbstract:Abstract The mechanisms of the antidepressant activity of Forskolin and a novel water soluble Forskolin analog (NKH477) were studied using the forced swimming method in rats. Forskolin (0.01–0.1 mg/kg) and NKH477 (0.01–0.1 mg/kg) dose-dependently decreased ratings of immobility, with effects similar to those of amitriptyline treatment. The maximum effects of Forskolin and NKH477 were observed at 0.01 mg/kg dose which is 150 more times potent than that (15 mg/kg) of amitriptyline. At a high dose (1.0 mg/kg) of Forskolin and NKH477, the duration of immobility was returned to control levels. Forskolin and NKH477 did not influence the spontaneous locomotor activity at intraperitoneal injection doses from 0.01 to 1 mg/kg. Furthermore chronic administration with NKH477 at oral dose from 0.5 to 1.5 mg/kg significantly decreases the duration of immobility. These data indicate that both Forskolin and NKH477 have strong antidepressive potency, consistent with the hypothesis that elevation of the cAMP cascade system may have an important role in antidepressive effects.
Abdul Traish - One of the best experts on this subject based on the ideXlab platform.
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G-protein-coupled receptor agonists augment adenylyl cyclase activity induced by Forskolin in human corpus cavernosum smooth muscle cells.
Receptors & signal transduction, 1997Co-Authors: Abdul Traish, Gallant C, Goldstein IAbstract:The goal of this study was to investigate the synergistic effects between G-protein-coupled receptor agonists and Forskolin-induced activation of adenylyl cyclases, in cultured human corpus cavernosum smooth-muscle cells. Treatment of human corpus cavernosum smooth-muscle cells with Forskolin (0.1-10 microM) produced an increase in cAMP synthesis in a concentration-dependent manner. Forskolin-induced adenylyl cyclase activity was markedly augmented by prostaglandin E1 (PGE1) and its metabolite, PGE0, isoproterenol, carbachol, and phenylephrine. Augmentation of Forskolin-induced cAMP by PGE1, and PGE0 is probably mediated by prostaglandin E receptors (EP). Enhancement of Forskolin-induced cAMP synthesis by isoproterenol is mediated by beta-adrenergic receptors (beta-AR), since this activity was inhibited by propranolol. Stimulation of Forskolin-induced cAMP synthesis by carbachol is attributed to activation of muscarinic acetylcholine receptors (mAChR), as demonstrated by inhibition with atropine. The augmentation of Forskolin-induced cAMP synthesis by phenylephrine, an alpha1-adrenergic receptor (AR) agonist, however, was unexpected and cannot be attributed to increased intracellular Ca2+, since treatment of cells with either the Ca2+ ionophore, A23187, or 80 mM KCl did not affect Forskolin-induced cAMP synthesis. Stimulation of Forskolin-induced cAMP synthesis by phenylephrine is explained by its binding to beta-AR and activation of Gs protein, since this augmentation was inhibited by the beta-AR antagonist, propranolol. This observation was further supported by physiological studies in organ bath chambers, in which Forskolin-induced relaxation of precontracted corpus cavernosum strips was enhanced by phenylephrine. These studies suggest that synergism between agonist-induced cAMP synthesis and Forskolin is attributed to increased conformational stabilization of activated adenylyl cyclase catalytic domains by Forskolin and the Gs(alpha)-subunit of activated Gs proteins.