Modulation of cGMP Synthesis and Metabolism

2015 ◽  
pp. 355-375 ◽  
Author(s):  
Kristen J. Bubb ◽  
Adrian J. Hobbs ◽  
James R. Klinger
Keyword(s):  
Cgmp Synthesis

ChemInform Abstract: Novel Pyridopyrimidine Derivatives as Inhibitors of Stable Toxin a (STa) Induced cGMP Synthesis.

ChemInform ◽  
2009 ◽  
Vol 40 (42) ◽  
Author(s):  
Eric A. Tanifum ◽  
Alexander Y. Kots ◽  
Byung-Kwon Choi ◽  
Ferid Murad ◽  
Scott R. Gilbertson
Keyword(s):  
Toxin A ◽  
Cgmp Synthesis

scholarly journals Calcium Feedback to cGMP Synthesis Strongly Attenuates Single-Photon Responses Driven by Long Rhodopsin Lifetimes

Neuron ◽  
2013 ◽  
Vol 78 (5) ◽  
pp. 949
Author(s):  
Owen P. Gross ◽  
Edward N. Pugh ◽  
Marie E. Burns
Keyword(s):  
Single Photon ◽  
Cgmp Synthesis

scholarly journals SERCA Cys674 sulphonylation and inhibition of L-type Ca2+ influx contribute to cardiac dysfunction in endotoxemic mice, independent of cGMP synthesis

2013 ◽  
Vol 305 (8) ◽  
pp. H1189-H1200 ◽  
Author(s):  
Ion A. Hobai ◽  
Emmanuel S. Buys ◽  
Justin C. Morse ◽  
Jessica Edgecomb ◽  
Eric H. Weiss ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Cardiac Dysfunction ◽  
Ryanodine Receptors ◽  
Soluble Guanylyl Cyclase ◽  
Wild Type ◽  
Cellular Mechanisms ◽  
Channel Current ◽  
Lps Challenge ◽  
Cgmp Synthesis ◽  
Phospholamban Phosphorylation

The goal of this study was to identify the cellular mechanisms responsible for cardiac dysfunction in endotoxemic mice. We aimed to differentiate the roles of cGMP [produced by soluble guanylyl cyclase (sGC)] versus oxidative posttranslational modifications of Ca2+ transporters. C57BL/6 mice [wild-type (WT) mice] were administered lipopolysaccharide (LPS; 25 μg/g ip) and euthanized 12 h later. Cardiomyocyte sarcomere shortening and Ca2+ transients (ΔCai) were depressed in LPS-challenged mice versus baseline. The time constant of Ca2+ decay (τCa) was prolonged, and sarcoplasmic reticulum Ca2+ load (CaSR) was depressed in LPS-challenged mice (vs. baseline), indicating decreased activity of sarco(endo)plasmic Ca2+-ATPase (SERCA). L-type Ca2+ channel current ( ICa,L) was also decreased after LPS challenge, whereas Na+/Ca2+ exchange activity, ryanodine receptors leak flux, or myofilament sensitivity for Ca2+ were unchanged. All Ca2+-handling abnormalities induced by LPS (the decrease in sarcomere shortening, ΔCai, CaSR, ICa,L, and τCa prolongation) were more pronounced in mice deficient in the sGC main isoform (sGCα1−/− mice) versus WT mice. LPS did not alter the protein expression of SERCA and phospholamban in either genotype. After LPS, phospholamban phosphorylation at Ser16 and Thr17 was unchanged in WT mice and was increased in sGCα1−/− mice. LPS caused sulphonylation of SERCA Cys674 (as measured immunohistochemically and supported by iodoacetamide labeling), which was greater in sGCα1−/− versus WT mice. Taken together, these results suggest that cardiac Ca2+ dysregulation in endotoxemic mice is mediated by a decrease in L-type Ca2+ channel function and oxidative posttranslational modifications of SERCA Cys674, with the latter (at least) being opposed by sGC-released cGMP.

GABAA, but not NMDA, receptors modulate in vivo NO-mediated cGMP synthesis in the rat cerebral cortex

2004 ◽  
Vol 46 (4) ◽  
pp. 480-489 ◽  
Author(s):  
Olimpia Pepicelli ◽  
Alessandra Brescia ◽  
Elisa Gherzi ◽  
Maurizio Raiteri ◽  
Ernesto Fedele
Keyword(s):  
Cerebral Cortex ◽  
Nmda Receptors ◽  
Rat Cerebral Cortex ◽  
Cgmp Synthesis

NO-dependent and NO-independent cGMP synthesis in cortical cholinergic neurons of the rat brain

2004 ◽  
pp. 551-553
Author(s):  
J de Vente ◽  
WCG van Staveren ◽  
M Ittersum ◽  
H Steinbusch
Keyword(s):  
Rat Brain ◽  
Cholinergic Neurons ◽  
Cgmp Synthesis

Effects of ANF on cGMP synthesis in inner medullary collecting duct subsegments of rats

1990 ◽  
Vol 259 (3) ◽  
pp. F535-F538
Author(s):  
K. Ujiie ◽  
H. Nonoguchi ◽  
K. Tomita ◽  
F. Marumo
Keyword(s):  
Atrial Natriuretic Factor ◽  
Collecting Duct ◽  
Target Site ◽  
Cyclic Monophosphate ◽  
Inner Medullary Collecting Duct ◽  
Camp Synthesis ◽  
Target Sites ◽  
Medullary Collecting Duct ◽  
Cgmp Synthesis ◽  
Major Target

The inner medullary collecting duct (IMCD) is thought to be a major target site for atrial natriuretic factor (ANF) action. The IMCD is divided into two subsegments (IMCD1, outer third; and IMCD2,3, inner two-thirds) based on differences in urea and water permeability. IMCD1 has similar characteristics to the outer medullary collecting duct (OMCD). To elucidate whether there are any differences among these segments in ANF actions, we investigated the effects of ANF on guanosine 3',5'-cyclic monophosphate (cGMP) synthesis in IMCD subsegments and the OMCD. We also examined the effects of arginine vasopressin (AVP) on adenosine 3',5'-cyclic monophosphate (cAMP) synthesis. IMCD subsegments (IMCD1,2,3) and OMCD were microdissected; and ANF-stimulated cGMP synthesis and AVP-stimulated cAMP synthesis were measured. cGMP synthesis stimulated by 10(-6) M ANF in IMCD1,2,3 (0.78 +/- 0.15, 0.81 +/- 0.19, 0.62 +/- 0.10 fmol.mm-1 x 3 min-1, mean +/- SE respectively, n = 10-11) was significantly (greater than 20-fold) higher than that in OMCD (0.03 +/- 0.02 fmol.mm-1 x 3 min-1, n = 7), and there was no difference among IMCD subsegments. On the other hand, cAMP synthesis stimulated by 10(-7) M AVP in IMCD subsegments was similar to that in OMCD. We conclude that IMCD is homogenous as a target site of ANF and is clearly distinguished from OMCD. In addition, more than half of ANF-stimulated cGMP synthesis in IMCD are considered to occur in IMCD1, simply because IMCD1 is dominant in population among IMCD subsegments. As target sites of AVP, IMCD subsegments are similar to OMCD.

scholarly journals Large Conductance Ca2+-Activated and Voltage-Activated K+ Channels Contribute to the Rise and Maintenance of Estrogen-Induced Uterine Vasodilation and Maintenance of Blood Pressure

Endocrinology ◽  
2012 ◽  
Vol 153 (12) ◽  
pp. 6012-6020 ◽  
Author(s):  
Charles R. Rosenfeld ◽  
Timothy Roy
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Uterine Artery ◽  
K Channel ◽  
Uterine Blood Flow ◽  
K Channels ◽  
Channel Inhibition ◽  
Estradiol 17Β ◽  
Cgmp Synthesis

Abstract Uterine blood flow (UBF) increases greater than 4-fold 90 min after systemic estradiol-17β (E2β) in nonpregnant sheep and remains elevated longer than 6–8 h; mean arterial pressure (MAP) is unchanged. Large-conductance Ca+2-activated (BKCa) and voltage-activated (KV) K+ channels contribute to the acute rise in UBF; their role in maintaining UBF and MAP longer than 90 min is unknown. We examined this in five nonpregnant, ovariectomized ewes with uterine artery (UA) flow probes and catheters in a UA for infusion of K+ channel inhibitors and uterine vein to sample venous effluent. Animals received systemic E2β (1.0 μg/kg; control), E2β+UA tetraethylammonium (TEA; 0.4–0.8 mm, n = 4), and E2β+UA 4-aminopyridine (4-AP; 0.01–0.08 mm, n = 4) to block BKCa and KV, respectively, while monitoring MAP, heart rate, and UBF. Uterine cGMP synthesis was measured. Ninety minutes after E2β, UBF rose 4.5-fold, uterine vascular resistance (UVR) fell greater than 5-fold and MAP was unchanged [78 ± 0.8 (sem) vs. 77 ± 1.5 mm Hg] in control studies and before UA inhibition with TEA and 4-AP. Between 90 and 120min, UBF, UVR, and MAP were unchanged after E2β alone. E2β+TEA dose dependently decreased ipsilateral UBF and increased UVR (24 ± 8.9 and 38 ± 16%, respectively, at 0.8 mm; P < 0.03); MAP was unchanged. Contralateral UBF/UVR were unaffected. E2β+4-AP also dose dependently decreased ipsilateral UBF and increased UVR (27 ± 5.3 and 76 ± 18%, respectively, at 0.08 mm; P < 0.001); however, MAP rose 27 ± 6.9% (P ≤ 0.006). E2β increased uterine cGMP synthesis greater than 3.5-fold and was unaffected by local K+ channel inhibition. BKCa and KV contribute to the rise and maintenance of E2β-induced uterine vasodilation, which is partially cGMP dependent. Systemic vascular KV also contributes to maintaining MAP after systemic E2β.

scholarly journals Calcium Feedback to cGMP Synthesis Strongly Attenuates Single-Photon Responses Driven by Long Rhodopsin Lifetimes

Neuron ◽  
2012 ◽  
Vol 76 (2) ◽  
pp. 370-382 ◽  
Author(s):  
Owen P. Gross ◽  
Edward N. Pugh ◽  
Marie E. Burns
Keyword(s):  
Single Photon ◽  
Cgmp Synthesis

scholarly journals Prolonged uterine artery nitric oxide synthase inhibition modestly alters basal uteroplacental vasodilation in the last third of ovine pregnancy

2014 ◽  
Vol 307 (8) ◽  
pp. H1196-H1203 ◽  
Author(s):  
Charles R. Rosenfeld ◽  
Timothy Roy
Keyword(s):  
Nitric Oxide ◽  
Uterine Artery ◽  
No Synthase ◽  
Uterine Horn ◽  
Signaling Systems ◽  
Uteroplacental Blood Flow ◽  
Dose Responses ◽  
Oxide Synthase ◽  
Cgmp Synthesis ◽  
In Pregnancy

Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain unclear, but they likely involve several integrated signaling systems. Endothelium-derived nitric oxide (NO) is considered an important contributor, but the extent of its involvement is unclear. Bolus intra-arterial infusions of nitro-l-arginine methyl ester (l-NAME) modestly decrease ovine basal UPBF; however, the doses and duration of infusion may have been insufficient. We, therefore, examined prolonged uterine artery (UA) NO synthase inhibition with l-NAME throughout the last third of ovine pregnancy by performing either continuous 30-min UA infusion dose responses ( n = 4) or 72-h UA infusions (0.01 mg/ml) at 104–108, 118–125, and 131–137 days of gestation ( n = 7) while monitoring mean arterial pressure (MAP), heart rate (HR), and UPBF. Uteroplacental vascular resistance (UPVR) was calculated, and uterine cGMP synthesis was measured. Thirty-minute UA l-NAME infusions did not dose dependently decrease UPBF, increase UPVR, or decrease uterine cGMP synthesis ( P > 0.1); however, MAP rose and HR fell modestly. Prolonged continuous 72-h UA l-NAME infusions decreased UPBF ∼32%, increased UPVR ∼68% ( P ≤ 0.001), and decreased uterine cGMP synthesis 70% at 54–72 h ( P ≤ 0.004); the noninfused uterine horn was unaffected. These findings were associated with ∼10% increases in MAP and decreases in HR that were greater at 104–108 than 118–125 and 131–137 days of gestation ( P = 0.006). Although uterine and UA NO and cGMP synthesis increase severalfold during ovine pregnancy, they contribute modestly to the maintenance and rise in UPBF in the last third of gestation. Thus, local UA NO may primarily modulate vasoconstrictor responses. Notably, the systemic vasculature appears more sensitive than the uterine vasculature to NO synthase inhibition.

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