2010
DOI: 10.1016/j.ejphar.2010.06.026
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Genistein, a competitive PDE1–4 inhibitor, may bind on high-affinity rolipram binding sites of brain cell membranes and then induce gastrointestinal adverse effects

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Cited by 6 publications
(3 citation statements)
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“…In clinical trials, compared to subjects receiving a placebo, subjects receiving genistein (54 mg/day for 2 years) revealed a significantly (19% versus 8%, P = .002) higher incidence of discontinued therapy following adverse gastrointestinal events, such as abdominal pain, epigastric pain, dyspepsia, and constipation [67]. In a murine model of allergic asthma, we also reported that genistein concentration-dependently inhibited 2 nM [ 3 H]-rolipram bound to HARBSs of brain cell membranes and shortened xylazine/ketamine-induced anesthesia at a dose level of 100  μ mol/kg (s.c.), suggesting that higher doses of genistein may induce adverse gastrointestinal side effects [68]. However, in the present results, biochanin A, even at 300  μ mol/kg (s.c.), did not shorten this kind of anesthesia.…”
Section: Discussioncontrasting
confidence: 70%
See 1 more Smart Citation
“…In clinical trials, compared to subjects receiving a placebo, subjects receiving genistein (54 mg/day for 2 years) revealed a significantly (19% versus 8%, P = .002) higher incidence of discontinued therapy following adverse gastrointestinal events, such as abdominal pain, epigastric pain, dyspepsia, and constipation [67]. In a murine model of allergic asthma, we also reported that genistein concentration-dependently inhibited 2 nM [ 3 H]-rolipram bound to HARBSs of brain cell membranes and shortened xylazine/ketamine-induced anesthesia at a dose level of 100  μ mol/kg (s.c.), suggesting that higher doses of genistein may induce adverse gastrointestinal side effects [68]. However, in the present results, biochanin A, even at 300  μ mol/kg (s.c.), did not shorten this kind of anesthesia.…”
Section: Discussioncontrasting
confidence: 70%
“…significantly enhanced the total serum IgG 2a levels, which had probably switched from IgM due to an increase in IFN- γ level [40, 41]. The increased IFN- γ levels may have been offset by genistein, which has recently been reported to inhibit IFN- γ levels [68], when biochanin A is demethylated. These results suggest that 24~50 h after oral administration, biochanin A is demethylated to produce genistein.…”
Section: Discussionmentioning
confidence: 99%
“…We next increased intracellular cAMP levels by inhibiting the cAMP-hydrolysing activity of Pde4 (Weiss, 1975), of which OPCs express several subtypes (Whitaker et al, 2008). Recently, a number of different Pde4 inhibitors have been used in preclinical studies (Nials et al, 2011;Schafer et al, 2010) and in clinical trials (Shih et al, 2010;Spina, 2008). To test whether small-molecule inhibitors of Pde4 can promote OPC differentiation in the presence of OPC differentiation inhibitors, Pde4 inhibitors (rolipram, milrinone, irsogladine, zaprinast and rottlerin) were added to the medium at various concentrations (Supporting Information Fig 3).…”
Section: Resultsmentioning
confidence: 99%