Endothelin receptors and angiotensin II receptors in tumor tissue.
In cancer chemotherapy, selective enhancement of drug delivery to tumor tissue is essentially important for increase of chemotherapeutic effects. An attenuated vasoconstrictive response to angiotensin II (Ang II) in tumors and a marked increase in tumor blood flow were observed compared with normal tissues during systemic hypertension induced by Ang II infusion. The phenomenon was absent when hypertension was provoked by endothelin-1 (ET-1). We assessed this response to characterize ET receptor and Ang II receptor density and affinity in normal and tumor tissues. The tumor cell line LY80 was transplanted to the skin in nude rats. Four weeks later the rats were sacrificed. [125I] ET-1 and [125I Sar1, Ile8]-Ang II were used to map the receptors for ET and Ang II in rat tissues using computerized in vitro autoradiography. A moderately high density of ET receptors, (ETB > ETA) was found in tumors. The Ang II receptors were markedly reduced in tumor tissues without changes in the affinity. These results suggest that the decrease in Ang II receptors but not ET receptors in tumors may explain the hemodynamic effect of Ang II-induced hypertension and ET-induced hypertension on tumor blood flow.
Kohzuki
M
M
Section of Internal Medicine and Disability Prevention, Tohoku University Graduate School of Medicine, Sendai, Japan.
Tanda
S
S
Hori
K
K
Yoshida
K
K
Kamimoto
M
M
Wu
X M
XM
Sato
T
T
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D017690:Cell Transplantation / Q000502:physiology; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation / Q000502:physiology; D009374:Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism*; D014183:Transplantation, Heterologous / Q000502:physiology; D014407:Tumor Cells, Cultured
D011945:Receptors, Angiotensin; D017466:Receptors, Endothelin; D000804:Angiotensin II