Author/Editor		Čemažar, Maja; Wilson, John; Prise, Vivien E; Hill, Sally A; Tozer, Gillian M
Title		Endothelin ETB receptor agonist IRL 1620 cause a decrease in blood flow in the rat P22 tumour model
Type		članek
Source		In: 11th international conference on Tumor physiology and cancer treatment; 2000 Oct 5-7; Banff, Alberta. Banff: ,
Publication year		2000
Volume		str. 93-4
Language		eng
Abstract		Summary: Endothelin-1 (ET-1) is a vasoactive peptide with diverse biological actions (Stjernquist et al. Cell Tissue Res 1998;292:1-9). Its action is modulated via two groups of receptors, namely ETA and ETB receptors (Arai et al. Nature 1990;348:730-2; Sakurai et al. Nature 1990; 348:732-5). The action of ET-1 on ETB receptors on vascular smooth muscle cells causes vasoconstriction, whereas vasodilatation can also be produced via stimulation of ETB receptors on endothelial cells (Shetty et al. Biochem Biophys Res Comm 1993;191:459-64.) The development of highly specific agonists and antagonists for ET-1 receptors provide a tool to determine the role of ET-1 in tumour vasculature and also to selectively modify tumour blood flow. The potential role of endothelin analogues as tumour blood flow modifiers is still relafiively unknown. In this study, we showed that P22 tumours were responsive to ETB agonist IRL 1620. Blood flow was reduced immediately after the intravenous (i.v.) bolus injection of IRL 1620. This reduction was reflected in increased tumour vascular resistance, thus indicating the constrictive capacity of tže drug. In addition, 125 I-ET-1 binding followed by autoradiography demonstrated the existence of both, ETA and ETB receptors in P22 tumours. Collectively, our results suggest that ETB receptors are localised on vascular smooth muscle rather than on endothelial cells and showed that activation of ETB receptors could be used for modifying tumour blood flow for therapeutical purpose. Methods: In the study the P22 rat carcinosarcoma implanted in the left flank of BD9 rats was used. Tumour blood flow was measured after bolus i.v. injection of 3 nmol/kg of IRL 1620 by laser Doppler flowmetry and by autoradiography of tumours following administration of radiolabelled iodoantipyrine (14C-IAP). (Abstract truncated at 2000 characters).
Descriptors		RECEPTORS, ENDOTHELIN ENDOTHELIN-1 CARCINOSARCOMA RATS LASER-DOPPLER FLOWMETRY AUTORADIOGRAPHY BLOOD PRESSURE TIME FACTORS