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  • Endothelin ETB receptor agonist IRL 1620 cause a decrease in blood flow in therat P22 tumour model
    Čemažar, Maja ...
    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 responsiveto 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 byautoradiography demonstrated the existence of both, ETA and ETB receptors inP22 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 laserDoppler flowmetry and by autoradiography of tumours following administration of radiolabelled iodoantipyrine (14C-IAP). (Abstract truncated at 2000 characters).
    Vir: Eleventh International Conference, Banff, Alberta, Canada, October 5-7, 2000 : Tumor Physiology and Cancer Treatment (Str. 93-94)
    Vrsta gradiva - prispevek na konferenci
    Leto - 2000
    Jezik - angleški
    COBISS.SI-ID - 15059673

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