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Effects of the polyamine spermine on arterial chemoreception

Cayzac, S., Rocher, A., Obeso, A., Gonzalez, C., Kemp, Paul J. ORCID: https://orcid.org/0000-0003-2773-973X and Riccardi, Daniela ORCID: https://orcid.org/0000-0002-7322-3163 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 (648) Netherlands: Springer Netherlands, pp. 97-104. 10.1007/978-90-481-2259-2_11

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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.

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: 19 Oct 2022 08:40
URI: https://orca.cardiff.ac.uk/id/eprint/18686

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