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Title: Role of polyamines in the carotid body
Author: Cayzac, Sebastien H.
ISNI:       0000 0004 2751 7181
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2008
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Polyamines are small organic molecules which modulate many physiological processes. Here, an inhibitory effect of spermine on rat carotid body chemoreception is reported. Spermine inhibits catecholamine release, from isolated carotid bodies, induced either by high K+ or by hypoxia. This inhibitory effect could be mediated by: the activation of the Ca2+ sensing receptor (CaR) or the inhibition of the voltage-dependent Ca2+ channels. Measurements of intracellular Ca2+ in dissociated type 1 cells, demonstrated that spermine inhibits Ca2+ influx evoked by either high K+ or hypoxia, but did not affect the resting intracellular Ca2+ levels. Then, the expression of the voltage-dependent Ca2+ channels and CaR were assessed by reverse-transcription polymerase chain reaction and immunochemistry in the carotid body. Cav1.2 and Cav2.2 were found to be especially expressed in type 1 cells while Cav1.3, Cav1.4, Cav2.1, Cav2.3, Cav3.1, Cav3.2 and Cav3.3 could not be detected. CaR was detected only in the nerve ending. Having declined a role of the CaR in mediating the spermine inhibition of type 1 cell chemoreception, the effect of spermine on Cav1.2 was investigated using patch-clamp recording of HEK293 cells transiently or stably expressing human Cav1.2. Spermine inhibits Cav1.2 using 2 mM Ba2+ as a charge carrier but not with 20 mM Ba2+. The inhibition of Cav1.2 by spermine in type 1 cells was then confirmed by co-application with nifedipine using Ca2+ imaging. These experiments demonstrate an inhibitory effect of spermine on Cav1.2 and potentially Cav2.2 in rat type 1 cells. In conclusion, spermine inhibits catecholamine release by type 1 cells, via the direct inhibition of Cav1.2 and possibly Cav2.2. This mechanism could act as a negative feedback on the type 1 cells and limit neurotransmitter release.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available