Cyclic cytidine 3',5'-monophosphate (cCMP) signals via cGMP kinase I.
We analysed the function and intracellular signalling of the cyclic pyrimidinic nucleotide cCMP. The membrane-permeable cCMP analogue dibutyryl-cCMP mediated mouse aorta relaxation. cCMP activated purified cGMP-dependent protein kinase (cGK) Iα and Iβ and stimulated cGK in aorta lysates. cCMP-induced relaxation was abolished in cGKI-knockout tissue. Additionally, deletion of inositol-trisphosphate receptor associated cGKI substrate (IRAG) suppressed cCMP-mediated relaxation. Signalling of cCMP via cGKI/IRAG appears to be of broader physiological importance because cCMP-mediated inhibition of platelet aggregation was absent in cGKI- and IRAG-deficient platelets. These results demonstrate that cCMP acts as intracellular messenger molecule, most unexpectedly utilizing the cGMP signal transduction pathway.
Desch
Matthias
M
Pharmacology and Toxicology, University Regensburg, Regensburg, Germany.
Schinner
Elisabeth
E
Kees
Frieder
F
Hofmann
Franz
F
Seifert
Roland
R
Schlossmann
Jens
J
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D003563:Cyclic CMP / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction
D053496:Inositol 1,4,5-Trisphosphate Receptors; D003563:Cyclic CMP; D017869:Cyclic GMP-Dependent Protein Kinases