scholarly journals Effect of neuronal nitric oxide synthase serine-1412 phosphorylation on hypothalamic–pituitary–ovarian function and leptin response

2020 ◽  
Vol 102 (6) ◽  
pp. 1281-1289 ◽  
Author(s):  
Damian D Guerra ◽  
Rachael Bok ◽  
Evelyn Llerena Cari ◽  
Cari Nicholas ◽  
David J Orlicky ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Estrous Cycle ◽  
Ovarian Function ◽  
Neuronal Nitric Oxide Synthase ◽  
Cycle Duration ◽  
Wild Type ◽  
Female Reproduction ◽  
Organ Systems ◽  
Oxide Synthase

Abstract Hypothalamic neuronal nitric oxide synthase (nNOS) potentiates adult female fertility in rodents by stimulating gonadotropin releasing hormone (GnRH) secretion, which in turn promotes luteinizing hormone (LH) release and ovulation. The mechanism of hypothalamic nNOS activation is not clear but could be via nNOS serine1412 (S1412) phosphorylation, which increases nNOS activity and physiologic NO effects in other organ systems. In female rodents, hypothalamic nNOS S1412 phosphorylation reportedly increases during proestrus or upon acute leptin exposure during diestrus. To determine if nNOS S1412 regulates female reproduction in mice, we compared the reproductive anatomy, estrous cycle duration and phase proportion, and fecundity of wild-type and nNOS serine1412➔alanine (nNOSS1412A) knock-in female mice. We also measured hypothalamic GnRH and serum LH, follicle stimulating hormone (FSH), estradiol, and progesterone in diestrus mice after intraperitoneal leptin injection. Organ weights and histology were not different by genotype. Ovarian primordial follicles, antral follicles, and corpora lutea were similar for wild-type and nNOSS1412A mice. Likewise, estrous cycle duration and phase length were not different, and fecundity was unremarkable. There were no differences among genotypes for LH, FSH, estradiol, or progesterone. In contrast to prior studies, our work suggests that nNOS S1412 phosphorylation is dispensable for normal hypothalamic–pituitary–ovarian function and regular estrous cycling. These findings have important implications for current models of fertility regulation by nNOS phosphorylation.

Localization of Ovarian Neuronal Nitric Oxide Synthase(NOS1) During the Ovine Estrous Cycle.

2009 ◽  
Vol 81 (Suppl_1) ◽  
pp. 561-561
Author(s):  
John A. McCracken ◽  
Thomas A. Hoagland ◽  
David T. Schreiber ◽  
Kuni Mah ◽  
Christopher S. Keator ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Estrous Cycle ◽  
Neuronal Nitric Oxide Synthase ◽  
Oxide Synthase

Prolactin promotes oxytocin and vasopressin release by activating neuronal nitric oxide synthase in the supraoptic and paraventricular nuclei

2010 ◽  
Vol 299 (6) ◽  
pp. R1701-R1708 ◽  
Author(s):  
Claudia Vega ◽  
Bibiana Moreno-Carranza ◽  
Miriam Zamorano ◽  
Andrés Quintanar-Stéphano ◽  
Isabel Méndez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Anterior Pituitary ◽  
Neuronal Nitric Oxide Synthase ◽  
Male Rats ◽  
Female Reproduction ◽  
Vasopressin Release ◽  
Hypothalamic Nuclei ◽  
Pituitary Glands ◽  
Oxide Synthase

Prolactin (PRL) stimulates the secretion of oxytocin (OXT) and arginine AVP as part of the maternal adaptations facilitating parturition and lactation. Both neurohormones are under the regulation of nitric oxide. Here, we investigate whether the activation of neuronal nitric oxide synthase (nNOS) in the hypothalamo-neurohypophyseal system mediates the effect of PRL on OXT and AVP release and whether these effects operate in males. Plasma levels of OXT and AVP were measured in male rats after the intracerebroventricular injection of PRL or after inducing hyperprolactinemia by placing two anterior pituitary glands under the kidney capsule. NOS activity was evaluated in the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei by NADPH-diaphorase histochemistry and in hypothalamic extracts by the phosphorylation/inactivation of nNOS at Ser847. Elevated central and systemic PRL correlated with increased NOS activity in the PVN and SON and with higher OXT and AVP circulating levels. Notably, treatment with 7-nitroindazole, a selective inhibitor of nNOS, prevented PRL-induced stimulation of the release of both neurohormones. Also, phosphorylation of nNOS was reduced in hyperprolactinemic rats, and treatment with bromocriptine, an inhibitor of anterior pituitary PRL secretion, suppressed this effect. These findings suggest that PRL enhances nNOS activity in the PVN and SON, thereby contributing to the regulation of OXT and AVP release. This mechanism likely contributes to the regulation of processes beyond those of female reproduction.

scholarly journals Lack of contribution of nitric oxide synthase to cholinergic vasodilation in murine renal afferent arterioles

2018 ◽  
Vol 314 (6) ◽  
pp. F1197-F1204 ◽  
Author(s):  
Sungmi Park ◽  
Benjamin J. Bivona ◽  
Lisa M. Harrison-Bernard
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Knockout Mice ◽  
Neuronal Nitric Oxide Synthase ◽  
Macula Densa ◽  
Afferent Arteriole ◽  
Wild Type ◽  
Afferent Arterioles ◽  
Nos Inhibitor ◽  
Oxide Synthase

We have previously reported significant increases in neuronal nitric oxide synthase (NOS) immunostaining in renal arterioles of angiotensin type 1A receptor (AT1A) knockout mice, and in arterioles and macula densa cells of AT1A/AT1B knockout mice. The contribution of nitric oxide derived from endothelial and macula densa cells in the maintenance of afferent arteriolar tone and acetylcholine-induced vasodilation was functionally determined in kidneys of wild-type, AT1A, and AT1A/AT1B knockout mice. Acetylcholine-induced changes in arteriolar diameters of in vitro blood-perfused juxtamedullary nephrons were measured during control conditions, in the presence of the nonspecific NOS inhibitor, Nω-nitro-l-arginine methyl ester (NLA), or the highly selective neuronal NOS inhibitor, N5-(1-imino-3-butenyl)-l-ornithine (VNIO). Acetylcholine (0.1 mM) produced a significant vasoconstriction in afferent arterioles of AT1A/AT1B mice (−10.9 ± 5.1%) and no changes in afferent arteriolar diameters of AT1A knockout mice. NLA (0.01–1 mM) or VNIO (0.01–1 μM) induced significant dose-dependent vasoconstrictions (−19.8 ± 4.0% 1 mM NLA; −7.8 ± 3.5% 1 μM VNIO) in afferent arterioles of kidneys of wild-type mice. VNIO had no effect on afferent arteriole diameters of AT1A knockout or AT1A/AT1B knockout mice, suggesting nonfunctional neuronal nitric oxide synthase. These data indicate that acetylcholine produces a significant renal afferent arteriole vasodilation independently of nitric oxide synthases in wild-type mice. AT1A receptors are essential for the manifestation of renal afferent arteriole responses to neuronal nitric oxide synthase-mediated nitric oxide release.

Effects of Targeted Neuronal Nitric Oxide Synthase Gene Disruption and Nitro sup G -L-Arginine Methylester on the Threshold for Isoflurane Anesthesia

1995 ◽  
Vol 83 (1) ◽  
pp. 101-108. ◽  
Author(s):  
Fumito Ichinose ◽  
Paul L. Huang ◽  
Warren M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Knockout Mice ◽  
Minimum Alveolar Concentration ◽  
Neuronal Nitric Oxide Synthase ◽  
Separate Experiment ◽  
Wild Type ◽  
Isoflurane Anesthesia ◽  
Congenital Deficiency ◽  
Oxide Synthase

Background Considerable evidence suggests that nitric oxide plays a role in synaptic transmission in the central and peripheral nervous system. Nonselective inhibition of nitric oxide synthase by nitroG-L-arginine methylester (L-NAME) reduces the minimum alveolar concentration of halothane anesthesia. The effects of selective neuronal nitric oxide synthase inhibition on the anesthetic requirements in mice congenitally deficient in neuronal nitric oxide synthase (knockout mice) were examined. Methods Isoflurane minimum alveolar concentration and righting reflex ED50 (RRED50) were determined in knockout and wild-type mice. Subsequently, the effects of intraperitoneal L-NAME on minimum alveolar concentration and RRED50 of knockout and wild-type mice were examined. In a separate experiment, the effects of week-long administration of L-NAME were examined in wild-type mice. Isoflurane minimum alveolar concentration and RRED50 were measured on the 8th day and were repeated after an acute intraperitoneal dose of L-NAME. Results Targeted disruption of the neuronal nitric oxide synthase gene did not modify isoflurane minimum alveolar concentration and RRED50 of knockout mice. Acute intraperitoneal L-NAME decreased the minimum alveolar concentration and RRED50 of wild-type but did not alter those values in knockout mice. The wild-type mice, when given L-NAME for a week, showed a minimum alveolar concentration and RRED50 identical to that of untreated wild-type mice. Conclusions Although acute nonselective inhibition of nitric oxide synthase reduces the anesthetic requirements of wild-type mice, a chronic congenital deficiency of neuronal nitric oxide synthase or a week of L-NAME treatment of wild-type mice does not produce a state of greater sensitivity to the effects of isoflurane anesthesia.

Neuronal nitric oxide synthase generates superoxide from the oxygenase domain

2001 ◽  
Vol 360 (1) ◽  
pp. 247-253 ◽  
Author(s):  
Hirohito YONEYAMA ◽  
Akira YAMAMOTO ◽  
Hiroaki KOSAKA
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Wild Type ◽  
Superoxide Generation ◽  
Superoxide Formation ◽  
Redox Active ◽  
Oxygenase Domain ◽  
Oxide Synthase ◽  
Reductase Domain

When l-arginine is depleted, neuronal nitric oxide synthase (nNOS) has been reported to generate superoxide. A flavoprotein module construct of nNOS has been demonstrated to be sufficient for superoxide production. In contrast, nNOS was reported not to be involved in superoxide formation, because such formation occurred with a mixture of the boiled enzyme and redox-active cofactors. We aimed to resolve these controversial issues by examining superoxide generation, without the addition of redox-active cofactors, by recombinant wild-type nNOS and by C415A-nNOS, which has a mutation in the haem proximal site. In a superoxide-sensitive adrenochrome assay, the initial lag period of C415A-nNOS was increased 2-fold compared with that of native nNOS. With ESR using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, prominent signals of the superoxide adduct were obtained with wild-type nNOS, whereas an enzyme preparation boiled for 5min did not produce superoxide. Higher concentrations of NaCN (10mM) decreased superoxide formation by 63%. Although the activity of the reductase domain was intact, superoxide generation from C415A-nNOS was decreased markedly, to only 10% of that of the wild-type enzyme. These results demonstrate that nNOS truly catalyses superoxide formation, that this involves the oxygenase domain, and that full-length nNOS hinders the reductase domain from producing superoxide.

Defective fluid and HCO3 − absorption in proximal tubule of neuronal nitric oxide synthase-knockout mice

2000 ◽  
Vol 279 (3) ◽  
pp. F518-F524 ◽  
Author(s):  
Tong Wang ◽  
Fiona M. Inglis ◽  
Robert G. Kalb
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Metabolic Acidosis ◽  
Nitric Oxide Synthase ◽  
Proximal Tubule ◽  
Knockout Mice ◽  
Neuronal Nitric Oxide Synthase ◽  
Fluid Absorption ◽  
Wild Type ◽  
Oxide Synthase

Using renal clearance techniques and in situ microperfusion of proximal tubules, we examined the effects of N G-monomethyl-l-arginine methyl ester (l-NAME) on fluid and HCO3 −transport in wild-type mice and also investigated proximal tubule transport in neuronal nitric oxide synthase (nNOS)-knockout mice. In wild-type mice, administration of l-NAME (3 mg/kg bolus iv) significantly increased mean blood pressure, urine volume, and urinary Na+ excretion. l-NAME, given by intravenous bolus and added to the luminal perfusion solution, decreased absorption of fluid (60%) and HCO3 − (49%) in the proximal tubule. In nNOS-knockout mice, the urinary excretion of HCO3 − was significantly higher than in the wild-type mice (3.12 ± 0.52 vs. 1.40 ± 0.33 mM) and the rates of HCO3 − and fluid absorption were 62 and 72% lower, respectively. Both arterial blood HCO3 − concentration (20.7 vs. 25.7 mM) and blood pH (7.27 vs. 7.34) were lower, indicating a significant metabolic acidosis in nNOS-knockout mice. Blood pressure was lower in nNOS-knockout mice (76.2 ± 4.6 mmHg) than in wild-type control animals (102.9 ± 8.4 mmHg); however, it increased in response to l-NAME (125.5 ± 5.07 mmHg). Plasma Na+ and K+ were not significantly different from control values. Our data show that a large component of HCO3 − and fluid absorption in the proximal tubule is controlled by nNOS. Mice without this isozyme are defective in absorption of fluid and HCO3 − in the proximal tubule and develop metabolic acidosis, suggesting that nNOS plays an important role in the regulation of acid-base balance.

Sign in / Sign up

Export Citation Format

Share Document