Expression of multidrug resistance proteins in rat and human chronic pancreatitis.
OBJECTIVE
The expression of the ABC-transporters MDR-1, MRP1, and MRP-2 was investigated in healthy pancreas and in chronic pancreatitis tissue samples in rats and humans to evaluate their possible involvement in a multidrug resistance of the pancreas with consequences for the pharmacologic treatment of pancreatic diseases.


METHODS
Human pancreatic tissue samples of healthy tissue and chronic pancreatitis were collected during pancreas surgery. In rats, the time-course of the expression of transporter proteins was studied 14, 28, and 56 days after experimental induction of chronic pancreatitis. The expression of MDR-1, MRP-1, MRP-2, and furthermore, LRP and PAP was investigated by RT-PCR, Real Time TaqManPCR, and immunohistochemistry.


RESULTS
In rat pancreas, MDR-1 (P-gp) and MRP-1 but in human pancreas MDR-1 (P-gp), MRP-1 and MRP-2 were found to be expressed. Chronic pancreatitis lead to an increased transcription of mRNA of MDR-1 (rat and human) and much lower, MRP-2 (human).


CONCLUSIONS
The expression of P-gp and related transporters could have impact on the metabolism, distribution, and availability of various compounds, including drugs, in the pancreas. The results indicate that this could be more pronounced in chronic pancreatitis.
Schaarschmidt
Thomas
T
Institute of Clinical Pharmacology, University of Rostock, Germany.
Merkord
Jutta
J
Adam
Ulrich
U
Schroeder
Eike
E
Kunert-Keil
Christiane
C
Sperker
Bernhard
B
Drewelow
Bernd
B
Wacke
Rainer
R
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002648:Child; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1