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Effects of the polyamine spermine on arterial chemoreception

Cayzac, S., Rocher, A., Obeso, A., Gonzalez, C., Kemp, Paul J. and Riccardi, Daniela 2009. Effects of the polyamine spermine on arterial chemoreception. Presented at: International Society of Arterial Chemoreception. 17th Meeting, Valladolid, Spain, 1-5 July 2008. Published in: Gonzalez, Constancio, Nurse, Colin A. and Peers, Chris eds. Arterial chemoreceptors. Advances in Experimental Medicine and Biology , vol. 648. Netherlands: Springer Netherlands, pp. 97-104. 10.1007/978-90-481-2259-2_11

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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.

Item Type: Conference or Workshop Item (Paper)
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: carotid body ; polyamine ; calcium sensing receptor ; spermine ; calcium channels ; catecholamine
Publisher: Springer Netherlands
ISBN: 9789048122585
Last Modified: 04 Jun 2017 03:14

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