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  • 2000-2004  (2)
  • 2003  (2)
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  • 2000-2004  (2)
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  • 1
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Omeprazole 10 mg is used as maintenance therapy for gastro-oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression.Aim : To evaluate the potency of acid suppression with omeprazole 10 mg, in relation to CYP2C19 genotypes.Methods : Eighteen healthy subjects without Helicobacter pylori participated. After a 7-day regimen of omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H2-receptor antagonist) or water only (baseline data), intragastric pH was measured for 24 h.Results : With omeprazole 10 mg, greater differences were observed than 20 mg in median pH values and pH 〉 4 holding time ratios between poor metabolizers (PMs, n = 6) and the others [homozygous extensive metabolizers (homo-EMs, n = 6) and heterozygous extensive metabolizers (hetero-EMs, n = 6)]. With lafutidine 20 mg, these parameters were not influenced by the genotype. The potency of acid suppression was: omeprazole 20 mg ≈ lafutidine 20 mg 〉 omeprazole 10 mg in homo-EMs, omeprazole 20 mg 〉 omeprazole 10 mg ≈ lafutidine 20 mg in hetero-EMs, and omeprazole 20 mg ≈ omeprazole 10 mg 〉 lafutidine 20 mg in PMs.Conclusions : Omeprazole 10 mg strongly suppresses acid secretion, but depending on the CYP2C19 genotypes shows greater interindividual variations in suppression than 20 mg.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have previously reported that voltage-dependent Ca2+ (VDC) channels of rat melanotrophs are inhibited by prostaglandin E2 (PGE2). In this study, mechanisms involved in the inhibitory actions of PGE2 receptors of rat melanotrophs were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR), Ca2+-imaging and whole-cell, patch-clamp techniques with recently developed EP agonists, each of which is selective for the known four subclasses of EP receptors (EP1–4). PGE2 reversibly suppressed the cytosolic Ca2+ concentration ([Ca2+]i). The maximum reduction in [Ca2+]i by PGE2 was comparable to that by dopamine or to that by extracellular Ca2+ removal. RT-PCR analysis of all four EP receptors revealed that EP3 and EP4 receptor mRNAs were expressed in the intermediate lobe. The effects of PGE2 to suppress [Ca2+]i were mimicked by the selective EP3 agonist, ONO-AE-248, whereas three other EP agonists, ONO-DI-004 (EP1), ONO-AE1-259 (EP2) and ONO-AE1-329 (EP4), had little or no effect on [Ca2+]i. All four G-protein activated inward rectifying K+ (GIRK) channel mRNAs were identified in intermediate lobe tissues by RT-PCR. Dopamine concentration-dependently activated GIRK currents, whereas PGE2 did not activate GIRK currents, even at the concentration causing maximal inhibition of VDC channels. These results suggest that PGE2 acts on EP3 receptors to suppress Ca2+ entry of rat melanotrophs by selectively inhibiting VDC channels of these cells. We have compared the possible cellular and molecular mechanisms of inhibition by dopamine and PGE2.
    Type of Medium: Electronic Resource
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