Abstract
Activation of cell-surface receptors often evokes changes in Ca2+ fluxes leading to an increase in cytosolic Ca2+, a generally accepted mediator of many cell responses1–3. The molecular mechanisms by which surface agonists elicit these changes in Ca2+ flux have remained elusive. An increase in the polyamines putrescine, spermidine and spermine, and their rate-regulating, synthetic enzyme ornithine decarboxylase (ODC), is one of the earliest events that occur during cell growth, replication and differentiation4–6. However, the precise physiological roles of the polyamines remain enigmatic4–6. Recently, we found that testosterone induces an early (<60s), Ca2+- and receptor-dependent stimulation of endocytosis, hexose transport and amino acid transport in mouse kidney cortex involving the proximal tubules7. This response is associated with increased Ca2+ fluxes and a mobilization of intracellular calcium, and is thought to represent a direct, receptor-mediated action of testosterone on the surface membrane7,8. Polyamine synthesis was previously found to be essential for the long-term effects of testosterone on mouse kidney9. We now report that testosterone evokes a rapid (<30 s), transient increase in ODC activity and a sustained increase in polyamines in kidney cortex. This polyamine synthesis is obligatory for stimulation of membrane transport functions and Ca2+ fluxes. These findings form the basis for a new theory of information flow in stimulus–response coupling in which the polyamines serve as messengers to generate a Ca2+ signal by increasing Ca2+ influx and mobilizing intracellular calcium via a cation-exchange reaction.
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Koenig, H., Goldstone, A. & Lu, C. Polyamines regulate calcium fluxes in a rapid plasma membrane response. Nature 305, 530–534 (1983). https://doi.org/10.1038/305530a0
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DOI: https://doi.org/10.1038/305530a0
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