Abstract
Polyamines modulate many biological functions. Here we report a novel inhibitory modulation by spermine of catecholamine release by the rat carotid body and have identified the molecular mechanism underpinning it. We used molecular (RT-PCR and confocal microscopy) and functional (i.e., neurotransmitter release, patch clamp recording and calcium imaging) approaches to test the involvement of: (i) voltage-dependent calcium channels, and; (ii) the extracellular calcium-sensing receptor, CaR, a G protein-coupled receptor which is also activated by polyamines. RT-PCR and immunohistochemistry of isolated carotid bodies revealed that only Cav1.2 and Cav2.2 were expressed in type 1 cells while Cav1.3, Cav1.4, Cav2.1, Cav2.3 and Cav3.1, Cav3.2 and Cav3.3, could not be detected. CaR expression was detected exclusively in the nerve endings. In isolated carotid bodies, the hypoxia-dependent (7% O2 for 10 minutes) and depolarization-evoked catecholamine release were partially suppressed by pre- (and co)-incubation with 500µM spermine. In dissociated type 1 glomus cells intracellular calcium concentration did not change following spermine treatment, but this polyamine did inhibit the depolarisation-evoked calcium influx. Whole-cell patch clamp recordings of HEK293 cells stably transfected with Cav1.2 demonstrated that spermine inhibits this calcium channel. Interestingly, this inhibition was not apparent if the extracellular solution contained a concentration of Ba2 above 2 mM as the charge carrier. In conclusion, spermine attenuates catecholamine release by the carotid body principally via inhibition of Cav1.2. This mechanism may represent a negative feedback, which limits transmitter release during hypoxia.
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Casero, R. A., Jr. & Marton, L. J. (2007) Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov, 6, 373–90.
Chaisiri, P., Harper, M. E. & Griffiths, K. (1979) Plasma spermine concentrations of patients with benign and malignant tumours of the breast or prostate. Clin Chim Acta, 92, 273–82.
Conde, S. V., Caceres, A. I., Vicario, I., Rocher, A., Obeso, A. & Gonzalez, C. (2006a) An overview on the homeostasis of Ca2+ in chemoreceptor cells of the rabbit and rat carotid bodies. Adv Exp Med Biol, 580, 215–22; discussion 351–9.
Conde, S. V., Obeso, A., Vicario, I., Rigual, R., Rocher, A. &Gonzalez, C. (2006b) Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors. J Neurochem, 98, 616–28.
Dogan, A., Rao, A. M., Hatcher, J., Rao, V. L., Baskaya, M. K. & Dempsey, R. J. (1999) Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion. J Neurochem, 72, 765–70.
E Silva, M. J. & Lewis, D. L. (1995) L- and N-type Ca2+ channels in adult rat carotid body chemoreceptor type I cells. J Physiol, 489(Pt 3), 689–99.
Fage, D., Voltz, C., Scatton, B. & Carter, C. (1992) Selective release of spermine and spermidine from the rat striatum by N-methyl-D-aspartate receptor activation in vivo. J Neurochem, 58, 2170–5.
Fearon, I. M., Zhang, M., Vollmer, C. & Nurse, C. A. (2003) GABA mediates autoreceptor feedback inhibition in the rat carotid body via presynaptic GABAB receptors and TASK-1. J Physiol, 553, 83–94.
Gilad, V. H., Halperin, R., Chen-Levy, Z. & Gilad, G. M. (2002) Cyclic changes of plasma spermine concentrations in women. Life Sci, 72, 135–41.
Gomez, M. & Hellstrand, P. (1995) Effects of polyamines on voltage-activated calcium channels in guinea-pig intestinal smooth muscle. Pflugers Arch, 430, 501–7.
Gonzalez, C., Almaraz, L., Obeso, A. & Rigual, R. (1994) Carotid body chemoreceptors: from natural stimuli to sensory discharges. Physiol Rev, 74, 829–98.
Heby, O. (1986) Putrescine, spermidine and spermine. NIPS, 1, 3.
Kemp, P. J., Peers, C., Riccardi, L., Iles, D. E., Mason, H. S., Wootton, P. & Williams, S. E. (2006) In search of the acute oxygen sensor: functional proteomics and acute regulation of large-conductance, calcium-activated potassium channels by hemeoxygenase-2. Adv Exp Med Biol, 580, 137–46; discussion 351–9.
Lasater, E. M. & Solessio, E. (2002) Regulation of voltage-sensitive Ca2+ channels in bipolar cells by divalent cations and polyamines. Adv Exp Med Biol, 514, 275–89.
Li, J., Doyle, K. M. & Tatlisumak, T. (2007) Polyamines in the brain: distribution, biological interactions, and their potential therapeutic role in brain ischaemia. Curr Med Chem, 14, 1807–13.
Masuko, T., Kusama-Eguchi, K., Sakata, K., Kusama, T., Chaki, S., Okuyama, S., Williams, K., Kashiwagi, K. & Igarashi, K. (2003) Polyamine transport, accumulation, and release in brain. J Neurochem, 84, 610–7.
Quinn, S. J., Ye, C. P., Diaz, R., Kifor, O., Bai, M., Vassilev, P. & Brown, E. (1997) The Ca2+ a target for polyamines. Am J Physiol, 273, C1315–23.
Ruat, M., Molliver, M. E., Snowman, A. M. & Snyder, S. H. (1995) Calcium sensing receptor: molecular cloning in rat and localization to nerve terminals. Proc Natl Acad Sci USA, 92, 3161–5.
Tabor, C. W. & Tabor, H. (1984) Polyamines. Annu Rev Biochem, 53, 749–90.
Vizard, T. N., O’keeffe, G. W., Gutierrez, H., Kos, C. H., Riccardi, D. & Davies, A. M. (2008) Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor. Nat Neurosci, 11, 285–91.
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Cayzac, S., Rocher, A., Obeso, A., Gonzalez, C., Kemp, P., Riccardi, D. (2009). Effects of the Polyamine Spermine on Arterial Chemoreception. In: Gonzalez, C., Nurse, C.A., Peers, C. (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 648. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2259-2_11
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DOI: https://doi.org/10.1007/978-90-481-2259-2_11
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