title: Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors.
abstract: 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.
authors.affiliation: Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD 21287-3200, USA.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Nunes
authors.forename: Andrew P S
authors.initials: AP
authors.lastname: Holmes
authors.forename: Vedangi
authors.initials: V
authors.lastname: Sample
authors.forename: Prem
authors.initials: P
authors.lastname: Kumar
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Cann
authors.forename: Emília C
authors.initials: EC
authors.lastname: Monteiro
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Estelle B
authors.initials: EB
authors.lastname: Gauda
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000262:Adenylyl Cyclases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000494:pharmacology*; D002344:Carotid Body / Q000166:cytology / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017950:Ganglia, Sensory / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000201:enzymology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009712:Nucleotides, Cyclic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001639:Bicarbonates; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D009712:Nucleotides, Cyclic; D012333:RNA, Messenger; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases
keywords: 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