Regulation of Cytosolic Guanylyl Cyclase by Nitric Oxide: The NO-Cyclic GMP Signal Transduction System

1994 ◽  
pp. 19-33 ◽  
Author(s):  
Ferid Murad
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Signal Transduction System

Isoforms of Nitric Oxide Synthase and the Nitric Oxide-Cyclic Gmp Signal Transduction System

1993 ◽  
pp. 73-80 ◽  
Author(s):  
Ferid Murad ◽  
U. Förstermann ◽  
M. Nakane ◽  
J. Pollock ◽  
H. Schmidt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Nitric Oxide Synthase ◽  
Cyclic Gmp ◽  
Signal Transduction System ◽  
Oxide Synthase

scholarly journals Dissection of a Hypoxia-induced, Nitric Oxide–mediated Signaling Cascade

2009 ◽  
Vol 20 (18) ◽  
pp. 4083-4090 ◽  
Author(s):  
Pascale F. Dijkers ◽  
Patrick H. O'Farrell
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Signaling Cascade ◽  
S2 Cells ◽  
Signal Transduction System ◽  
Signaling Systems ◽  
Calcium Dependent ◽  
Drosophila S2 Cells ◽  
Oxide Synthase ◽  
Multiple Signaling

Befitting oxygen's key role in life's processes, hypoxia engages multiple signaling systems that evoke pervasive adaptations. Using surrogate genetics in a powerful biological model, we dissect a poorly understood hypoxia-sensing and signal transduction system. Hypoxia triggers NO-dependent accumulation of cyclic GMP and translocation of cytoplasmic GFP-Relish (an NFκB/Rel transcription factor) to the nucleus in Drosophila S2 cells. An enzyme capable of eliminating NO interrupted signaling specifically when it was targeted to the mitochondria, arguing for a mitochondrial NO signal. Long pretreatment with an inhibitor of nitric oxide synthase (NOS), L-NAME, blocked signaling. However, addition shortly before hypoxia was without effect, suggesting that signaling is supported by the prior action of NOS and is independent of NOS action during hypoxia. We implicated the glutathione adduct, GSNO, as a signaling mediator by showing that overexpression of the cytoplasmic enzyme catalyzing its destruction, GSNOR, blocks signaling, whereas knockdown of this activity caused reporter translocation in the absence of hypoxia. In downstream steps, cGMP accumulated, and calcium-dependent signaling was subsequently activated via cGMP-dependent channels. These findings reveal the use of unconventional steps in an NO pathway involved in sensing hypoxia and initiating signaling.

Novel guanylyl cyclase inhibitor, ODQ reveals role of nitric oxide, but not of cyclic GMP in endothelin-1 secretion

FEBS Letters ◽  
1995 ◽  
Vol 376 (3) ◽  
pp. 262-266 ◽  
Author(s):  
Friedrich Brunner ◽  
Heike Stessel ◽  
Walter R. Kukovetz
Keyword(s):  
Nitric Oxide ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Endothelin 1

NADPH diaphorase activity in the antennae of the hawkmoth Manduca sexta

1996 ◽  
Vol 199 (5) ◽  
pp. 1063-1072 ◽  
Author(s):  
M Stengl ◽  
R Zintl
Keyword(s):  
Nitric Oxide ◽  
Manduca Sexta ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Pupal Stage ◽  
Histochemical Staining ◽  
Nadph Diaphorase ◽  
Positive Staining ◽  
Receptor Cells ◽  
Diaphorase Activity

Biochemical and physiological studies suggested that increases in the levels of cyclic GMP in insect antennal receptor cells play a role in olfactory adaptation. As inositol-trisphosphate-dependent Ca2+ influx appears to precede the increase in intracellular cyclic GMP levels, it was hypothesized that a Ca2+-dependent mechanism might stimulate the guanylyl cyclase. The present study used histochemical staining for NADPH diaphorase to examine whether antennal receptor neurones of male Manduca sexta could contain nitric oxide synthase. This Ca2+/calmodulin-dependent enzyme is a prerequisite for nitric-oxide-dependent stimulation of guanylyl cyclase and possesses NADPH diaphorase activity. It was found that a subpopulation of olfactory receptor neurones as well as mechano-, thermo- and hygroreceptors on the moth antenna are NADPH-diaphorase-positive. Staining was also seen in non-neuronal cells. In the developing antenna, the NADPH-diaphorase-dependent staining was first observed at pupal stage 13-14, at approximately the same time as the antennal receptor neurones became physiologically active. The number and location of stained receptor cells was highly variable, and significantly more pheromone-sensitive sensilla were NADPH-diaphorase-positive in pheromone-stimulated antennae. This suggests that the enzyme is transiently activated by pheromone rather than being continuously active.

Inhibition of nitrovasodilator- and acetylcholine-induced relaxation and cyclic GMP accumulation by the cytochrome P-450 substrate, 7-ethoxyresorufin

1992 ◽  
Vol 70 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Brian M. Bennett ◽  
Bernard J. McDonald ◽  
Rita Nigam ◽  
Patrick G. Long ◽  
W. Craig Simon
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Competitive Inhibition ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Endothelial Nitric Oxide ◽  
Cytochrome P 450

We examined the effect of the cytochrome P-450 substrate, 7-ethoxyresorufin (7-ER), and its corresponding product, resorufin, on nitrovasodilator- and endothelium-dependent relaxation of isolated rat aorta. The EC50 value for glyceryl trinitrate (GTN) induced relaxation was increased over 100-fold by 7-ER and less than 3-fold by resorufin. The EC50 value for sodium nitroprusside (SNP) induced relaxation was increased approximately 12-fold by 7-ER, acetylcholine (ACh) induced relaxation was abolished, and relaxation induced by isopropylnorepinephrine was not significantly affected. GTN-, SNP-, and ACh-induced increases in cyclic GMP accumulation were inhibited by 7-ER, as were basal cyclic GMP levels in endothelium-intact, but not endothelium-denuded tissues. 7-ER decreased GTN biotransformation in intact aorta and decreased the regioselective formation of glyceryl-1,2-dinitrate. The activation by GTN and SNP of aortic guanylyl cyclase in broken cell preparations was not affected by 7-ER, indicating that the inhibitory effect of 7-ER is probably not due to a direct interaction with guanylyl cyclase. The inhibitory effect of 7-ER on GTN-induced relaxation was not altered by the addition of superoxide dismutase, suggesting that 7-ER does not act by increasing superoxide anion concentration (which would serve to increase the degradation of nitric oxide (NO) formed during vascular GTN biotransformation). Our data provide further evidence for the role of the cytochrome P-450 – cytochrome P-450 reductase system in the biotransformation of GTN to an activator (presumably nitric oxide) of guanylyl cyclase. The data are consistent with a mode of action of 7-ER involving either competitive inhibition of vascular cytochrome P-450 or uncoupling of vascular cytochrome P-450 reductase from cytochrome P-450. The data also suggest that the cytochrome P-450 system facilitates NO release from SNP and that 7-ER has an inhibitory effect on endothelial nitric oxide synthase.Key words: glyceryl trinitrate, nitrovasodilators, cytochrome P-450, vascular smooth muscle, 7-ethoxyresorufin, endothelium, cyclic GMP.

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