title: Soluble adenylyl cyclase accounts for high basal cCMP and cUMP concentrations in HEK293 and B103 cells.
abstract: Intact HEK293 cells and B103 neuroblastoma cells possess high basal concentrations of the established second messengers cAMP and cGMP and of the emerging second messengers cCMP and cUMP. We asked the question which nucleotidyl cyclase accounts for the high basal cNMP concentrations. Activators and inhibitors of soluble guanylyl cyclase had no major effects on cNMPs, and the activator of membranous adenylyl cyclase forskolin increased only cAMP. Addition of bicarbonate to medium increased, whereas removal of bicarbonate decreased levels of all four cNMPs. The inhibitor of soluble adenylyl cyclase, 2-(1H-benzo[d]imidazol-2-ylthio)-N'-(5-bromo-2-hydroxybenzylidene) propanehydrazide (KH7), reduced bicarbonate-stimulated cNMPs. In conclusion, bicarbonate-stimulated soluble adenylyl cyclase plays an important role in the regulation of basal cellular cNMP levels, most notably cCMP and cUMP.
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: hasan.alan@mh-hannover.de.
authors.forename: Alan
authors.initials: A
authors.lastname: Hasan
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: kerstin.danker@evotec.com.
authors.forename: Kerstin Y
authors.initials: KY
authors.lastname: Danker
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: wolter.sabine@mh-hannover.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wolter
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: baehre.heike@mh-hannover.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Bähre
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: kaever.volkhard@mh-hannover.de.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: seifert.roland@mh-hannover.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D003563:Cyclic CMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D057809:HEK293 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D014542:Uridine Monophosphate / Q000378:metabolism*
chemical_list: C000590972:2-(1H-benzo(d)imidazol-2-ylthio)-N'-(5-bromo-2-hydroxybenzylidene)propanehydrazide; D001562:Benzimidazoles; D001639:Bicarbonates; D004791:Enzyme Inhibitors; D006834:Hydrazines; D009712:Nucleotides, Cyclic; D018160:Receptors, Cytoplasmic and Nuclear; D005576:Colforsin; D003563:Cyclic CMP; C045338:cyclic 3',5'-uridine monophosphate; D014542:Uridine Monophosphate; C579271:ADCY10 protein, human; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase
keywords: Cyclic AMP; Cyclic CMP; Cyclic UMP; Membranous adenylyl cyclase; Soluble adenylyl cyclase