Espression of CYP3A Isoforms and P-Glycoprotein in Human Stomach, Jejunum and Ileum
| Autor: | Anders Rane, Loredana Serpe, Anna Nordmark, Mario Eandi, Roberto Canaparo, Elisabetta Muntoni, Gian Paolo Zara, N Finnstrom |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Genotype Physiology Ileum Gastroenterology Isozyme Jejunum Cytochrome P-450 Enzyme System Western blot Physiology (medical) Internal medicine medicine Cytochrome P-450 CYP3A Humans ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger Aged P-glycoprotein Aged 80 and over Pharmacology Messenger RNA biology medicine.diagnostic_test Stomach digestive oral and skin physiology Middle Aged Molecular biology Small intestine Isoenzymes medicine.anatomical_structure Gene Expression Regulation biology.protein Female Aryl Hydrocarbon Hydroxylases |
| Popis: | 1. CYP3A isoforms metabolise a diverse array of clinically important drugs and P-glycoprotein (P-gp), a transmembrane efflux pump, can extrude a wide variety of drugs from the cell. It has been suggested that the function of CYP3A4 is complementary to that of P-gp along the gastrointestinal (GI) tract, together forming a coordinated intestinal barrier against xenobiotics. Therefore, the expression of CYP3A4, CYP3A5, CYP3A7 and ABCB1 (P-gp) genes were quantified in five normal samples from the human stomach, seven from the jejunum and eight from the ileum by real-time reverse transcription-polymerase chain reaction and western blot analysis. 2. In the tissues examined, measurable mRNA expression of CYP3A was found in almost all samples from the stomach, jejunum and ileum. The rank order for CYP3A mRNA expression was CYP3A4 > CYP3A5 > CYP3A7 in the GI tract studied, whereas median mRNA CYP3A4 expression was highest in the small intestine and lowest in the stomach. Expression of ABCB1 mRNA was found in almost all samples and the median mRNA expression level was comparable in the jejunum and ileum, but lower in the stomach. Our data also show a significant correlation between all mRNA transcripts studied and a wide interindividual variation. 3. At the protein level, CYP3A4 was detected in all stomach and small intestine samples, the levels being substantially higher in the small intestine than in the stomach. P-Glycoprotein was detected in all GI samples, but no statistically significant difference was found along the GI tract considered. 4. Collectively, these results demonstrate that CYP3A4 is the main CYP3A expressed in the GI tract investigated, an extensive interindividual variability in the expression of the different CYP3A isoforms in all tissues examined and P-gp apoprotein levels similar in the stomach, jejunum and ileum. |
| Databáze: | OpenAIRE |
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