From canonical to non-canonical cyclic nucleotides as second messengers: pharmacological implications.

摘要: This review summarizes our knowledge on the non-canonical cyclic nucleotides cCMP, cUMP, cIMP, cXMP and cTMP. We place field into a historic context discuss unresolved questions future directions of research. implications for experimental clinical pharmacology, focusing bacterial infections, cardiovascular neuropsychiatric disorders reproduction medicine. The canonical purine cAMP cGMP fulfill criteria second messengers. (i) are synthesized by specific generators, i.e. adenylyl guanylyl cyclases, respectively. (ii) activate effector proteins, e.g. protein kinases. (iii) exert biological effects. (iv) effects terminated phosphodiesterases export. mimicked (v) membrane-permeable nucleotide analogs (vi) toxins. For decades, existence relevance cCMP cUMP have been controversial. Modern mass-spectrometric methods unequivocally demonstrated in mammalian cells. both, messenger molecules now fulfilled as well. There patterns which nucleotidyl cyclases generate cNMPs how they degraded exported, resulting unique cNMP signatures systems. signaling systems, specifically at level soluble cyclase, cyclase ExoY from Pseudomonas aeruginosa more promiscuous than previously appreciated. evolutionary new molecules, probably reflecting an adaption to requirements higher organisms.