Abstract
Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3',5'-monophosphate (cAMP). It has been assumed that bicarbonate mediates its effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro in a pH-independent manner. sAC is most similar to adenylyl cyclases from cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in these early forms of life. sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenylyl Cyclases / chemistry
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Adenylyl Cyclases / genetics
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Adenylyl Cyclases / isolation & purification
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Adenylyl Cyclases / metabolism*
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Animals
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Bicarbonates / metabolism*
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Bicarbonates / pharmacology
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Catalytic Domain
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Cell Line
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Cyanobacteria / enzymology
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Cyclic AMP / metabolism
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Enzyme Activation
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Evolution, Molecular
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Humans
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Hydrogen-Ion Concentration
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Male
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Phylogeny
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Rats
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Second Messenger Systems
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Signal Transduction
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Solubility
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Sperm Capacitation
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Spermatozoa / enzymology
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Spermatozoa / metabolism*
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Spermatozoa / physiology
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Testis / metabolism
Substances
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Bicarbonates
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Recombinant Proteins
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Cyclic AMP
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Adenylyl Cyclases