Two classes of antagonist interact with receptors for the mitogenic neuropeptides bombesin, bradykinin, and vasopressin.

Growth Factors
P J Woll, E Rozengurt

Abstract

While screening neuropeptides for activity as growth factors we have found that bradykinin is a mitogen for Swiss 3T3 cells. It acts synergistically with insulin, and maximal effect is obtained at 10 nM. It acts through a distinct receptor, characterized as a B2 subtype using bradykinin analogues. The neuropeptides bombesin and vasopressin are also potent mitogens for Swiss 3T3 cells. The substance P antagonists [DArg1, DPro2, DTrp7,9, Leu11] substance P and [DArg1, DPhe5, DTrp7,9, Leu11]substance P are inhibitors of DNA synthesis stimulated by both bombesin and vasopressin. In the present study they were found also to inhibit bradykinin-induced mitogenesis. In contrast, the ligand-specific antagonists [Leu13-psi(CH2NH)Leu14]bombesin, [Pmp1, OMeTyr2, Arg8]vasopressin and [DArg0, Hyp3, Thi5,8, DPhe7]bradykinin showed no cross-inhibition with each others receptors. We propose therefore that the receptors for the mitogenic neuropeptides bombesin, vasopressin, and bradykinin can interact with two classes of antagonist, one recognizing the ligand binding site (e.g., [Leu13-psi(CH2NH)Leu14]bombesin) and the other recognizing a common domain shared by the three receptors (e.g., [DArg1, DPhe5, DTrp7,9, Leu11]substance P).

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Citations

Dec 1, 1993·Journal of Cellular Biochemistry·G MünsI Rubinstein
Oct 1, 1996·Critical Reviews in Oncology/hematology·R de Castiglione, L Gozzini
Aug 30, 2002·Journal of Affective Disorders·Lucinda V Scott, Timothy G Dinan
Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·I ZacharyE Rozengurt
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·K SzepeshaziJ E Horvath
Dec 1, 1990·The American Review of Respiratory Disease·E Rozengurt
Sep 1, 1994·Journal of Cellular Physiology·K Kiehne, E Rozengurt
Jan 1, 1991·Cancer Investigation·V M Macaulay, D N Carney
Jan 1, 1993·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M J EverardI E Smith
Jan 1, 1991·Critical Reviews in Oncology/hematology·J Viallet, D C Ihde
Apr 1, 1991·European Journal of Clinical Investigation·E Rozengurt
Mar 12, 1990·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·E Rozengurt, J Sinnett-Smith
Aug 15, 2001·American Journal of Physiology. Cell Physiology·C SantiskulvongE Rozengurt

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