RGD Reference Report - The pharmacokinetics of morphine and its glucuronide conjugate in a rat model of streptozotocin-induced diabetes and the expression of MRP2, MRP3 and UGT2B1 in the liver. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

The pharmacokinetics of morphine and its glucuronide conjugate in a rat model of streptozotocin-induced diabetes and the expression of MRP2, MRP3 and UGT2B1 in the liver.

Authors: Hasegawa, Y  Kishimoto, S  Shibatani, N  Nomura, H  Ishii, Y  Onishi, M  Inotsume, N  Takeuchi, Y  Fukushima, S 
Citation: Hasegawa Y, etal., J Pharm Pharmacol. 2010 Mar;62(3):310-4. doi: 10.1211/jpp.62.03.0004.
RGD ID: 11541075
Pubmed: PMID:20487213   (View Abstract at PubMed)
DOI: DOI:10.1211/jpp.62.03.0004   (Journal Full-text)

OBJECTIVES: The aim was to investigate the pharmacokinetics of morphine and its metabolite, morphine-3-glucuronide (M3G), in a rat model of streptozotocin (STZ)-induced diabetes. METHODS: Morphine (15 mg/kg) was administered intravenously, and the concentrations of morphine and M3G in the plasma, urine and bile were measured by HPLC. Changes in the expression of multidrug resistance-associated proteins (MRP2 and MRP3) and UDP-glucuronosyltransferase 2B1 (UGT2B1) mRNA in the liver were also estimated by reverse-transcriptase PCR. KEY FINDINGS: Plasma morphine concentrations were lower in the STZ-diabetic rats than controls although the elimination half-life of morphine was similar in the two groups (47.9 +/- 10.7 min and 47.2 +/- 8.6 min, respectively). The concentration of M3G in plasma was higher in STZ-diabetic than control rats, and the biliary excretion of M3G was lower in the STZ-diabetic rats (7.4 +/- 2.3% vs 13.3 +/- 2.0%). The urinary excretion of M3G was similar in the two groups (10.1 +/- 6.8% vs 10.9 +/- 4.9%). The expression of MRP3 and UGT2B1 mRNA was increased in STZ-diabetic rats, whereas expression of MRP2 mRNA was decreased. CONCLUSIONS: In STZ-diabetic rats, the distribution volume of morphine increased, the glucuronidation rate and M3G transportation into the blood were enhanced, and the excretion of M3G was decreased, leading to an increase in the plasma M3G concentration.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOAbcc2 (Rattus norvegicus)11541075; 11541075mRNA:decreased expression:liverRGD 
Experimental Diabetes Mellitus  ISOAbcc3 (Rattus norvegicus)11541075; 11541075mRNA:increased expression:liverRGD 
Experimental Diabetes Mellitus  IEP 11541075mRNA:decreased expression:liverRGD 
Experimental Diabetes Mellitus  IEP 11541075; 11541075mRNA:increased expression:liverRGD 
Experimental Diabetes Mellitus  ISOUgt2b1 (Rattus norvegicus)11541075; 11541075mRNA:increased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc2  (ATP binding cassette subfamily C member 2)
Abcc3  (ATP binding cassette subfamily C member 3)
Ugt2b1  (UDP glucuronosyltransferase 2 family, polypeptide B1)

Genes (Mus musculus)
Abcc2  (ATP-binding cassette, sub-family member 2)
Abcc3  (ATP-binding cassette, sub-family C member 3)
Ugt2b1  (UDP glucuronosyltransferase 2 family, polypeptide B1)

Genes (Homo sapiens)
ABCC2  (ATP binding cassette subfamily C member 2)
ABCC3  (ATP binding cassette subfamily C member 3)
UGT2B17  (UDP glucuronosyltransferase family 2 member B17)


Additional Information