Influence of P-glycoprotein on pulmonary disposition of the model substrate [ < sup > 11 < /sup > C]metoclopramide assessed by PET imaging in rats
Eur J Pharm Sci. 2023 Feb 9:106404. doi: 10.1016/j.ejps.2023.106404. Online ahead of print.ABSTRACTIn the lungs, the membrane transporter P-glycoprotein (P-gp) is expressed in the apical (i.e. lumen-facing) membrane of airway epithelial cells and in the luminal (blood-facing) membrane of pulmonary capillary endothelial cells. To better understand the influence of P-gp on the pulmonary disposition of inhaled P-gp substrate drugs, we measured the intrapulmonary pharmacokinetics of the intratracheally (i.t.) aerosolized model P-gp substrate [11C]metoclopramide in presence and absence of P-gp activity by means of positron emis...
Source: European Journal of Pharmaceutical Sciences - February 11, 2023 Category: Drugs & Pharmacology Authors: Severin Mairinger Irene Hern ández-Lozano Thomas Filip Mathilde L öbsch Johann Stanek Markus Zeitlinger Marcus Hacker Nicolas Tournier Thomas Wanek Carsten Ehrhardt Oliver Langer Source Type: research
Influence of P-glycoprotein on pulmonary disposition of the model substrate [ < sup > 11 < /sup > C]metoclopramide assessed by PET imaging in rats
Eur J Pharm Sci. 2023 Feb 9:106404. doi: 10.1016/j.ejps.2023.106404. Online ahead of print.ABSTRACTIn the lungs, the membrane transporter P-glycoprotein (P-gp) is expressed in the apical (i.e. lumen-facing) membrane of airway epithelial cells and in the luminal (blood-facing) membrane of pulmonary capillary endothelial cells. To better understand the influence of P-gp on the pulmonary disposition of inhaled P-gp substrate drugs, we measured the intrapulmonary pharmacokinetics of the intratracheally (i.t.) aerosolized model P-gp substrate [11C]metoclopramide in presence and absence of P-gp activity by means of positron emis...
Source: European Journal of Pharmaceutical Sciences - February 11, 2023 Category: Drugs & Pharmacology Authors: Severin Mairinger Irene Hern ández-Lozano Thomas Filip Mathilde L öbsch Johann Stanek Markus Zeitlinger Marcus Hacker Nicolas Tournier Thomas Wanek Carsten Ehrhardt Oliver Langer Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Brazilian Journal of Medical and Biological Research - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Braz J Med Biol Res - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Small molecule inhibitors of intestinal epithelial anion exchanger SLC26A3 (DRA) with a luminal, extracellular site of action
Eur J Med Chem. 2023 Jan 27;249:115149. doi: 10.1016/j.ejmech.2023.115149. Online ahead of print.ABSTRACTThe anion exchanger protein SLC26A3 (down-regulated in adenoma, DRA) is expressed in the luminal membrane of intestinal epithelial cells in colon, where it facilitates the absorption of Cl- and oxalate. We previously identified a 4,8-dimethylcoumarin class of SLC26A3 inhibitors that act from the SLC26A3 cytoplasmic surface, and demonstrated their efficacy in mouse models of constipation and hyperoxaluria. Here, screening of 50,000 new compounds and 1740 chemical analogs of active compounds from the primary screen produc...
Source: European Journal of Medicinal Chemistry - February 1, 2023 Category: Chemistry Authors: Onur Cil Marc O Anderson Livia de Souza Goncalves Joseph-Anthony Tan Peter M Haggie Alan S Verkman Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Brazilian Journal of Medical and Biological Research - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Braz J Med Biol Res - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Brazilian Journal of Medical and Biological Research - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Braz J Med Biol Res - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Brazilian Journal of Medical and Biological Research - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Braz J Med Biol Res - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Brazilian Journal of Medical and Biological Research - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Braz J Med Biol Res - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Brazilian Journal of Medical and Biological Research - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
Luteolin ameliorates loperamide-induced functional constipation in mice
This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoact...
Source: Braz J Med Biol Res - February 1, 2023 Category: Research Authors: Yujin Wang Hua Jiang Lijun Wang Huiping Gan Xinchun Xiao Liangwu Huang Wenxin Li Zongrun Li Source Type: research
