Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective was to evaluate the expression of the multidrug resistance P-glycoprotein (P-gp) in peripheral blood lymphocytes (PBL) of patients with rheumatoid arthritis (RA). PBL from 68 RA patients and 44 controls were evaluated. RA patients had a mean disease duration of 10.7 yr, with a mean number of past resistances to DMARDs of 0.82, and were treated with NSAIDs (n = 34), DMARDs (n = 25) and prednisolone (n = 40). Fluorescence flow cytometry was used to assess P-gp membrane expression on PBL. In the RA group, the percentage of PBL expressing P-gp was higher in patients treated with prednisolone than in other patients [mean +/- S.D.: 10.7 +/- 15.8% vs 3.3 +/- 7.6%, P < 0.03, Student] and was not related to other therapies, age, sex, RA duration, number of past resistances to DMARDs, activity, ESR, CRP. The percentage of PBL expressing P-gp did not differ in RA and control groups, but was higher in the prednisolone-treated RA patients than in controls. Prednisolone could induce a rise in the percentage of PBL expressing P-gp. On the contrary, patients with a high percentage of PBL expressing P-gp could be more resistant to DMARDs and need prednisolone earlier. Further studies are needed to address this question and to evaluate the potential implication of P-gp in drug resistance in RA.
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PMID:Expression of the multidrug resistance glycoprotein 170 in the peripheral blood lymphocytes of rheumatoid arthritis patients. The percentage of lymphocytes expressing glycoprotein 170 is increased in patients treated with prednisolone. 864 32

The interaction between steroid hormones and intestinal P-glycoprotein was investigated by measuring intestinal absorption from rat small intestine in situ. Prednisolone and hydrocortisone were rapidly absorbed from the entire small intestine. In contrast, methylprednisolone absorption was significantly retarded in jejunum and ileum by an intestinal efflux system. In the presence of verapamil an quinidine, the retarded absorption of methylprednisolone was completely recovered, suggesting that P-glycoprotein is responsible for the unique features of methylprednisolone absorption. A requisite for the substrate of intestinal P-glycoprotein seemed to be 6 alpha-methyl group in the steroid structure. Substrate specificity of intestinal P-glycoprotein to steroid hormones was shown to be in part different from those in other tissues such as adrenal gland. Little of all three steroid hormones disappeared in the supernatant of mucosal homogenate from rat small intestine, indicating that intestinal metabolism of these steroid hormones was relatively small.
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PMID:Involvement of intestinal P-glycoprotein in the restricted absorption of methylprednisolone from rat small intestine. 945 71

We recently reported that P-glycoprotein (MDR1) is capable of interfering with the absorption of methylprednisolone in the rat small intestine. This study was undertaken to examine the interaction between methylprednisolone and MDR1 using Caco-2 cells. The permeation of various steroid hormones (hydrocortisone, prednisolone, progesterone, beta-estradiol, and testosterone) was compared. The basolateral-to-apical (secretory) permeation of methylprednisolone was more than 3-fold greater than the apical-to-basolateral (absorptive) permeation. When verapamil (0.1 mm), a potent modulator of MDR1, was added to both apical and basolateral sides of Caco-2 cells, the absorptive permeation of methylprednisolone was increased and its secretory permeation was decreased. As a result, the secretory-oriented manner of methylprednisolone permeation almost completely disappeared. Prednisolone and hydrocortisone exhibited weaker secretory-oriented movement than did methylprednisolone. The secretory-oriented permeation of prednisolone and hydrocortisone was also diminished by the addition of verapamil. There was no significant directionality in progesterone permeation and the permeation of beta-estradiol and testosterone tended to be absorptive. These results appear to suggest that methylprednisolone, prednisolone, and hydrocortisone interact with MDR1 as the substrates. In contrast, there was no evidence that MDR1 was capable of potently interfering with the absorption of the sex hormones tested in this study, supporting our previous findings in the rat. It was further found that apically-added verapamil demonstrated a modulating effect on MDR1 function even at 5 microM.
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PMID:Secretory transport of methylprednisolone possibly mediated by P-glycoprotein in Caco-2 cells. 1191 42

The present study aims to investigate the effects of prednisolone on the pharmacokinetics of orally and intravenously administered loratadine in rats. A single dose of loratadine was administered orally (4 mg/kg) and intravenously (1 mg/kg) in the presence or absence of prednisolone (0.2 or 0.8 mg/kg). Compared to the oral control group, prednisolone (0.2 mg/kg, p < 0.05; 0.8 mg/kg, p < 0.01) significantly increased the area under the plasma concentrationtime curve of orally administered loratadine by 54.0-96.4%. After oral administration, the peak plasma concentration of loratadine was significantly (0.2 mg/kg, p < 0.05; 0.8 mg/kg, p < 0.01) increased by 20.9-65.3% in the presence of prednisolone. Consequently, the relative bioavailability of loratadine was increased by 1.54- to 1.96-fold. Compared to the intravenous control group, the presence of prednisolone significantly (0.8 mg/kg, p < 0.05) increased the area under the plasma concentration-time curve of loratadine. Prednisolone enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine may be due to inhibition both cytochrome P450 3A4-mediated metabolism and the efflux pump P-glycoprotein (P-gp) in the intestine and/or liver by the presence of prednisolone.
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PMID:Effects of prednisolone on the pharmacokinetics of loratadine after oral and intravenous administration of loratadine in rats. 2094 38

Prednisolone is a glucocorticoid (GC) commonly used in the treatment of canine mast cell tumours (MCTs); however, resistance to GCs develops in many MCTs following repeated treatment. P-glycoprotein (P-gp), signal transducer and activator of transcription 3 (STAT3) and KIT (CD117) are involved in GC resistance. The aim of this study was to evaluate the response to prednisolone treatment in canine cutaneous MCTs and to investigate the levels of P-gp, STAT3, phospho-STAT3 (pSTAT3) and KIT proteins in MCTs with or without prednisolone treatment. Immunohistochemistry was performed on tumour samples from 41 dogs with cutaneous MCTs. The overall objective response rate (including complete and partial responses) was 51.8% for dogs treated with prednisolone; poorly differentiated or higher stage MCTs had a lower response rate. The median time-span of tumours to reach maximal tumour regression was 14 d (range 3-77 d); 22 (81.5%) reached maximal regression at 21 d. The majority of MCTs overexpressed both P-gp and STAT3 before and after prednisolone treatment. Reduced expression of pSTAT3 and alterations in the KIT expression pattern were observed in MCTs post-treatment. Prednisolone treatment that caused a marked reduction in tumour volume was correlated with reduced pSTAT3 expression. A cytoplasmic KIT staining pattern was correlated with a lower tumour response rate to prednisolone treatment.
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PMID:Overexpression of P-glycoprotein, STAT3, phospho-STAT3 and KIT in spontaneous canine cutaneous mast cell tumours before and after prednisolone treatment. 2239 32