scholarly journals Pharmacological profile of a nitric oxide donor spermine NONOate in the mouse corpus cavernosum

2014 ◽  
Vol 44 ◽  
pp. 569-575 ◽  
Author(s):  
Fatma Peyman ERTUĞ ◽  
Erğin ŞİNGİRİK ◽  
Hacer Sinem BÜYÜKNACAR ◽  
Cemil GÖÇMEN ◽  
Mehmet Ata SEÇİLMİŞ
Keyword(s):  
Nitric Oxide ◽  
Corpus Cavernosum ◽  
Nitric Oxide Donor ◽  
Pharmacological Profile ◽  
Spermine Nonoate ◽  
Mouse Corpus Cavernosum

Nitric oxide attenuates endothelin-1-induced vasoconstriction in canine stomach

1996 ◽  
Vol 271 (1) ◽  
pp. G27-G35
Author(s):  
J. G. Wood ◽  
Q. Zhang ◽  
Z. Y. Yan ◽  
L. Y. Cheung
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Ischemia Reperfusion ◽  
Nitric Oxide Donor ◽  
Question Mark ◽  
Endothelin 1 ◽  
Vasoconstrictor Response ◽  
Anesthetized Dogs ◽  
Spermine Nonoate

We previously observed that endothelin-1 (ET-1)-induced gastric vasoconstriction is enhanced after ischemia-reperfusion. The purpose of our present study was to examine the role of nitric oxide in regulating ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion. Using a mechanically perfused stomach segment from chloralose-anesthetized dogs, we examined 1) responses to NG-nitro-L-arginine methyl ester (L-NAME) alone and in combination with L-arginine, 2) whether L-NAME affects ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion, and 3) if spermine NONOate inverted question mark1,3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl; a nitric oxide donor inverted question mark attenuates the augmented response to ET-1 after ischemia-reperfusion. Our results show that 1) L-NAME significantly increased baseline vascular resistance and this response was reduced by L-arginine, 2) ET-1-induced vasoconstriction was enhanced by L-NAME, and 3) administration of spermine NONOate during reperfusion largely attenuated the vasoconstrictor response to ET-1 after ischemia-reperfusion. Our findings are consistent with the hypothesis that nitric oxide modulates responses to ET-1 under normal conditions, and loss of this vasodilator after ischemia-reperfusion results in an augmented response to ET-1.

Evidence that nitric oxide synthase is involved in progesterone-induced acrosomal exocytosis in mouse spermatozoa

1997 ◽  
Vol 9 (4) ◽  
pp. 433 ◽  
Author(s):  
María Beléen Herrero ◽  
J. Marcelo Viggiano ◽  
Silvina Pérez Martínez ◽  
Martha F. de Gimeno
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
No Synthase ◽  
Nitric Oxide Donor ◽  
Mouse Sperm ◽  
Acrosomal Exocytosis ◽  
Oxide Synthase ◽  
Spermine Nonoate

In a recent work, we detected nitric oxide synthase (NO synthase) in the acrosome and tail of mouse and human spermatozoa by an immunofluorescence technique. Also, NO-synthase inhibitors added during sperm capacitationin vitro reduced the percentage of oocytes fertilized in vitro, suggesting a role for NO synthase in sperm function. Therefore, in the present study the effect of three NO-synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-D-arginine methyl ester (D-NAME) and L-NG-nitro-arginine (NO2-arg), and of a nitric oxide donor, spermine-NONOate, on the progesterone-induced acrosome reaction of mouse sperm was examined. NO-synthase inhibitors were added at 0, 60 or 90 min during capacitation; at 120 min, mouse epididymal spermatozoa were exposed to 15 µM progesterone for another 15 min. In another set of experiments, different concentrations of spermine-NONOate were added to capacitated spermatozoa for 15 min; in these experiments, progesterone was not included. NO2-arg and L-NAME blocked progesterone-induced exocytosis regardless of the time at which these inhibitors were added. Moreover, D-NAME did not inhibit exocytosis. In contrast, spermine-NONOate stimulated the acrosomal exocytosis in vitro directly. These results provide evidence that mouse sperm NO synthase participates in the progesterone-induced acrosome reactionin vitro and that nitric oxide induces this event.

Guanylyl cyclase stimulatory coupling to KCachannels

2000 ◽  
Vol 279 (6) ◽  
pp. C1938-C1945 ◽  
Author(s):  
M. Nara ◽  
P. D. K. Dhulipala ◽  
G. J. Ji ◽  
U. R. Kamasani ◽  
Y.-X. Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Guanylyl Cyclase ◽  
Phosphorylation Site ◽  
Nitric Oxide Donor ◽  
Dependent Manner ◽  
Dependent Protein Kinase ◽  
Α Subunit ◽  
Dependent Protein ◽  
Spermine Nonoate

We coexpressed the human large-conductance, calcium-activated K (KCa) channel (α- and β-subunits) and rat atrial natriuretic peptide (ANP) receptor genes in Xenopus oocytes to examine the mechanism of guanylyl cyclase stimulatory coupling to the channel. Exposure of oocytes to ANP stimulated whole cell KCa currents by 21 ± 3% (at 60 mV), without altering current kinetics. Similarly, spermine NONOate, a nitric oxide donor, increased KCa currents (20 ± 4% at 60 mV) in oocytes expressing the channel subunits alone. Stimulation of KCacurrents by ANP was inhibited in a concentration-dependent manner by a peptide inhibitor of cGMP-dependent protein kinase (PKG). Receptor/channel stimulatory coupling was not completely abolished by mutating the cAMP-dependent protein kinase phosphorylation site on the α-subunit (S869; Nars M, Dhulipals PD, Wang YX, and Kotlikoff MI. J Biol Chem 273: 14920–14924, 1998) or by mutating a neighboring consensus PKG site (S855), but mutation of both residues virtually abolished coupling. Spermine NONOate also failed to stimulate channels expressed from the double mutant cRNAs. These data indicate that nitric oxide donors stimulate KCa channels through cGMP-dependent phosphorylation and that two serine residues (855 and 869) underlie this stimulatory coupling.

scholarly journals Nitric oxide inhibits sodium reabsorption in the isolated perfused cortical collecting duct.

1995 ◽  
Vol 6 (1) ◽  
pp. 89-94
Author(s):  
B A Stoos ◽  
N H Garcia ◽  
J L Garvin
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Collecting Duct ◽  
Indirect Evidence ◽  
Nitric Oxide Donor ◽  
Sodium Reabsorption ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Sodium Flux ◽  
Spermine Nonoate

Indirect evidence suggests that nitric oxide inhibits sodium reabsorption by the collecting duct; however, direct evidence is lacking. It was hypothesized that endothelium-derived nitric oxide inhibits sodium flux in the cortical collecting duct by blocking amiloride-sensitive sodium channels. Tubules were obtained from Sprague-Dawley rats pretreated with deoxycorticosterone acetate (5 mg/rat i.m.) 5 to 9 days before the experiment. Nitric oxide was added to the system by either the addition of endothelial cells and the induction of the release of nitric oxide via acetylcholine (10(-7) M) or by the addition of nitric oxide donors. Acetylcholine-induced nitric oxide release from endothelial cells decreased lumen-to-bath sodium flux by 24 +/- 7% (N = 3; P < 0.05). The addition of the nitric oxide donor, spermine NONOate (10(-5) M), decreased net sodium flux 68% from 10.1 +/- 2.0 to 3.6 +/- 2 pmol/mm.min (N = 5; P < 0.025). To assure that the inhibition of sodium flux was due to nitric oxide, another donor, nitroglycerin (2 x 10(-5) M), was used, which decreased sodium flux by 43%. Luminal amiloride (10 microM) decreased net sodium flux by 83% (from 14.8 +/- 1.2 to 2.4 +/- 0.7 pmol/mm.min; N = 5; P < 0.025). The addition of nitric oxide via spermine NONOate to tubules decreased intracellular sodium levels by 26% (N = 6; P < 0.005). The Na(+)-K+ATPase activity of spermine NONOate-treated tubules was 14.7 +/- 3.2 pmol/mm.min compared with the control value of 10.2 +/- 2.0 pmol/mm.min. Nitroglycerin did not significantly affect pump activity either.(ABSTRACT TRUNCATED AT 250 WORDS)

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