Regulation of nitric oxide-sensitive guanylyl cyclase.
In this review, we outline the current knowledge on the regulation of nitric oxide (NO)-sensitive guanylyl cyclase (GC). Besides NO, the physiological activator that binds to the prosthetic heme group of the enzyme, two novel classes of GC activators have been identified that may have broad pharmacological implications. YC-1 and YC-1-like substances act as NO sensitizers, whereas the substance BAY 58-2667 stimulates NO-sensitive GC NO-independently and preferentially activates the heme-free form of the enzyme. Sensitization and desensitization of NO/cGMP signaling have been reported to occur on the level of NO-sensitive GC; in the present study, an alternative mechanism is introduced explaining the adaptation of the NO-induced cGMP response by a long-term activation of the cGMP-degrading phosphodiesterase 5 (PDE5). Finally, regulation of GC expression and a possible modulation of GC activity by other factors are discussed.
Friebe
Andreas
A
Abteilung für Pharmakologie, Medizinische Fakultät, Ruhr-Universität Bochum, Universitätsstr. 150, 44780 Bochum, Germany. doris.koesling@ruhr-uni-bochum.de
Koesling
Doris
D
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase
D020536:Enzyme Activators; D007527:Isoenzymes; D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D002118:Calcium