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Cyclic AMP and Epac Contribute to the Genesis of the Positive Interaction Between Hypoxia and Hypercapnia in the Carotid Body

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Arterial Chemoreception

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 758))

Abstract

Carotid body chemoreceptor cells in response to hypoxic and hypercapnic stimulus increase their resting rate of release of neurotransmitters and their action potential frequency in the carotid sinus sensory nerve. When chemoreceptor activity is assessed at the level of the carotid sinus nerve and on ventilation, there exists an interaction between hypoxic and hypercapnic stimulus so that the response to both stimuli combined is additive or more than additive, over a wide range of stimulation. It is not clear if this interaction occurs at chemoreceptor cell or directly acting on the sensory nerve. In the present work we demonstrate for the first time the existence of a positive interaction between hypoxic and hypercapnic-acidotic stimuli at the level of both, membrane potential depolarization and neurotransmitter release in rat and rabbit carotid body. Inhibition of adenylate cyclase (SQ-22536) abolished the positive interaction between stimuli and the Epac (exchange proteins activated by cAMP) activator 8-pCPT-2′-O-Me-cAMP reversed the effect of adenylate cyclase inhibition. These results suggest that this interaction between the two natural stimuli is mediated by cAMP via an Epac-dependent pathway, at least at the level of neurotransmitter release.

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Acknowledgements

This work was supported by grants BFU2007-61848 (DGICYT), CIBER CB06/06/0050 (FISS-ICIII).

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Correspondence to Asuncion Rocher .

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© 2012 Springer Science+Business Media Dordrecht

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Ramirez, M., Almaraz, L., Gonzalez, C., Rocher, A. (2012). Cyclic AMP and Epac Contribute to the Genesis of the Positive Interaction Between Hypoxia and Hypercapnia in the Carotid Body. In: Nurse, C., Gonzalez, C., Peers, C., Prabhakar, N. (eds) Arterial Chemoreception. Advances in Experimental Medicine and Biology, vol 758. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4584-1_30

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