Abstract
Growth factors can be divided into two classes which act through distinct signal transduction pathways1. One class including epidermal growth factor, platelet derived growth factor and fibroblast growth factor activates receptor tyrosine kinases2,3, and the second class, including thrombin4,5, bombesin6,7, bradykinin7 and vasopressin7,8 activates a phosphoinositide-specific phospholipase C through GTP-binding proteins9 which can be inactivated by pertussis toxin10. In Chinese hamster lung fibroblasts, thrombin-induced mitogenicity seems to correlate well with phospholipase C activation and both events are sensitive to pertussis toxin1,5,11. Thrombin12,13, like the other mitogens in this class14–16, simultaneously inhibits adenylate cyclase. This involves an inhibitory G protein (Gi), a well established pertussis toxin substrate17,18. The relative contributions of the two signalling pathways to mitogenicity has not been evaluated so far. We report here that the neurotransmitter serotonin (5-hydroxytryptamine), a contracting agent19 and mitogen for smooth muscle cells20, activates phospholipase C, inhibits adenylate cyclase and stimulates DNA synthesis in fibroblasts. These events are sensitive to pertussis toxin. We show that the mitogenicity of 5-hydroxytryptamine can be uncoupled from phospholipase C activation that is mediated by 5-HT2 receptors, but correlates perfectly with inhibition of adenylate cyclase through 5-HT1B receptors. We propose that inhibition of adenylate cyclase or activation of an undefined effector system by Gi is important in 5-hydroxytryptamine induced DNA synthesis and contributes to the strong mitogenicity of the other members of this family of growth factors.
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Seuwen, K., Magnaldo, I. & Pouysségur, J. Serotonin stimulates DNA synthesis in fibroblasts acting through 5–HT1B receptors coupled to a Gi-protein. Nature 335, 254–256 (1988). https://doi.org/10.1038/335254a0
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DOI: https://doi.org/10.1038/335254a0
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