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Respir Physiol Neurobiol. 2013 Aug 15;188(2):83-93. doi: 10.1016/j.resp.2013.05.013. Epub 2013 May 31.

Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors.

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Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD 21287-3200, USA.


Stimulation of the carotid body (CB) chemoreceptors by hypercapnia triggers a reflex ventilatory response via a cascade of cellular events, which includes generation of cAMP. However, it is not known if molecular CO2/HCO3(-) and/or H(+) mediate this effect and how these molecules contribute to cAMP production. We previously reported that the CB highly expresses HCO3(-)-sensitive soluble adenylyl cyclase (sAC). In the present study we systematically characterize the role of sAC in the CB, comparing the effect of isohydric hypercapnia (IH) in cAMP generation through activation of sAC or transmembrane-adenylyl cyclase (tmAC). Pharmacological deactivation of sAC and tmAC decreased the CB cAMP content in normocapnia and IH with no differences between these two conditions. Changes from normocapnia to IH did not effect the degree of PKA activation and the carotid sinus nerve discharge frequency. sAC and tmAC are functional in CB but intracellular elevations in CO2/HCO3(-) in IH conditions on their own are insufficient to further activate these enzymes, suggesting that the hypercapnic response is dependent on secondary acidosis.


Adenylyl cyclase; CA; CB; CSN; Carotid body; FSK; G-protein coupled receptors.; GPCR; HCO(3)(−); Hypercapnia; IH; P; PG; PKA; SD rats; Sprague-Dawley rats; bicarbonate ion; cAMP; carbonic anhydrase; carotid body; carotid sinus nerve; forskolin; isohydric hypercapnia; petrosal ganglion; postnatal days; protein kinase A; sAC; soluble adenylyl cyclase; tmAC; transmembrane adenylyl cyclase

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