Bombesin impairs spindle function in mitotic V79 Chinese hamster cells by a receptor-dependent mechanism.
Bombesin belongs to a family of peptides acting as local hormones with roles in growth regulation, neural function and secretion. Upon binding to its receptor bombesin primarily elicits an increase of inositolphosphates and diacylglycerol, events leading to increased [Ca2+]i and activation of protein kinase C. When asynchronously growing V79 Chinese hamster cells were treated with bombesin in the 10(-9)-10(-7) M concentration range their content of inositolphosphates increased and so did the frequency of mitotic cells with abnormal chromosomal arrangements (c-mitoses). Both effects were abolished by simultaneous addition of the synthetic peptide antagonist D-Arg1,D-Phe5,D-Trpu7,9-Leu11-substance P that binds to certain bombesin receptors. These results demonstrate that the V79 cells most probably have receptors for bombesin and that the weak but significant c-mitotic effect is mediated by such receptors.
Onfelt
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Department of Genetic and Cellular Toxicology, Stockholm University, Sweden.
D000704:Analysis of Variance; D000818:Animals; D001839:Bombesin / Q000633:toxicity*; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D008938:Mitosis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects*; D013373:Substance P / Q000378:metabolism
D009153:Mutagens; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D013373:Substance P; D001839:Bombesin