Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2.
Carbon monoxide (CO) is a putative gaseous neurotransmitter that lacks vesicular storage and must be synthesized rapidly following neuronal depolarization. We show that the biosynthetic enzyme for CO, heme oxygenase-2 (HO2), is activated during neuronal stimulation by phosphorylation by CK2 (formerly casein kinase 2). Phorbol ester treatment of hippocampal cultures results in the phosphorylation and activation of HO2 by CK2, implicating protein kinase C (PKC) in CK2 stimulation. Odorant treatment of olfactory receptor neurons augments HO2 phosphorylation and activity as well as cyclic guanosine monophosphate (cGMP) levels, with all of these effects selectively blocked by CK2 inhibitors. Likewise, CO-mediated nonadrenergic, noncholinergic (NANC) relaxation of the internal anal sphincter requires CK2 activity. Our findings provide a molecular mechanism for the rapid neuronal activation of CO biosynthesis, as required for a gaseous neurotransmitter.
Boehning
Darren
D
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Moon
Cheil
C
Sharma
Sumit
S
Hurt
K Joseph
KJ
Hester
Lynda D
LD
Ronnett
Gabriele V
GV
Shugar
David
D
Snyder
Solomon H
SH
D000818:Animals; D019556:COS Cells; D002248:Carbon Monoxide / Q000378:metabolism*; D047390:Casein Kinase II; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000201:enzymology; D009924:Organ Culture Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D010703:Phorbol Esters; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases