Immunohistochemical expression of P-glycoprotein in the rat urinary bladder and the effect of verapamil on intravesical chemotherapy.
BACKGROUND
The expression of P-glycoprotein (Pgp) is thought to be common in bladder epithelium and the multidrug resistance mediated by Pgp must be considered to improve the efficacy of chemotherapy for bladder tumors.


METHODS
The expression of Pgp in normal and tumor tissue of the rat urinary bladder was first examined immunohistochemically. The effect of verapamil, an expected modulator of Pgp, on intravesical chemotherapy of the rats was then investigated.


RESULTS
Pgp was immunohistochemically detected in normal epithelium and in tumor tissue of the rat urinary bladder. In those normal and tumor-bearing bladders, verapamil promoted the uptake of intravesically instilled pirarubicin, but the efflux of intracellular accumulated pirarubicin was observed subsequently in both conditions with and without verapamil. The drug concentration decreased more rapidly in the verapamil group than in the control group.


CONCLUSIONS
Verapamil is thought to be useful in promoting uptake of intravesically instilled pirarubicin, but it did not appear to be so efficient at limiting the efflux of intracellular accumulated pirarubicin.
Department of Urology, Asahikawa Medical College, Asahikawa, Japan. hhiroshima@asahikawa-med.ac.jp
H
H
Hashimoto
M
M
Tokumitsu
Y
Y
Saga
M
M
Okuyama
S
S
Yachiku
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000283:Administration, Intravesical; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D005260:Female; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014700:Verapamil / Q000008:administration & dosage*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D014700:Verapamil