Protein kinase A increases electrical stimulation-induced neuronal nitric oxide release in rat mesenteric artery

Ferrer, Mercedes; Sánchez, Margarita; Martín, María Nieves Cabrera; Márquez-Rodas, Iván; Alonso, María J.; Salaíces, Mercedes; Balfagón, Gloria

doi:10.1016/j.ejphar.2004.01.030

Cited by 19 publications

(18 citation statements)

References 29 publications

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“…Petrofsky et al proposed that ES increases blood flow in the wound site through an increase in the release of the vasodilator NO [37]. In addition, Ferrer et al in an experimental study reported that ES induces vasodilation by release of NO [38]. The mechanism by which ES increases the NO plasma level is still not well understood.…”

Section: Discussionmentioning

confidence: 99%

Effect of low-intensity direct current on expression of vascular endothelial growth factor and nitric oxide in diabetic foot ulcers

et al. 2014

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Abstract-This study investigated the effect of low-intensity cathodal direct current on the release of plasma vascular endothelial growth factor (VEGF) and nitric oxide (NO) in diabetic foot ulceration. Twenty type 2 diabetic patients with foot ulceration and thirteen age-matched healthy subjects were enrolled. Patients were randomly assigned to electrical stimulation (ES) (n = 10) or sham ES (placebo, n = 10) groups. The ES group received cathodal direct current (1.48 +/-0.98 mA) for 1 h/d, 3 d/wk for 4 wk (12 sessions). Blood samples were collected for VEGF and NO measurement in the first and last treatment sessions before and after intervention. Wound surface area and skin temperature were measured at the 1st, 6th, and 12th sessions. VEGF significantly increased in the ES group compared with the placebo group after the 1st (106.61 +/-79.50 and 40.88 +/-26.20, respectively) and 12th sessions (109.28 +/-67.30 and 34.79 +/-13.20, respectively). NO level also increased significantly in the ES group compared with the placebo group after the 12th session (44.21 +/-14.00 and 35.25 +/-11.00, respectively). The increase of skin temperature was significantly higher in the ES group than the placebo group. Application of low-intensity ES increases the expression of VEGF and NO, which may lead to improved blood flow and tissue temperature and, consequently, wound healing in diabetic foot ulceration.

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Section: Discussionmentioning

confidence: 99%

Effect of low-intensity direct current on expression of vascular endothelial growth factor and nitric oxide in diabetic foot ulcers

et al. 2014

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“…In this respect, it is possible to speculate that very subtle differences could exist in the modulation of NOS isoforms, i.e. regulatory mechanisms other than PKC could be working on eNOS, including different redox conditions (Polytarchou & Papadimitriou 2005), phosphatase activity (Fleming et al 2001) and/ or other kinases (Ferrer et al 2004) that, in turn, regulate the intracellular environment and function.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C activation increases endothelial nitric oxide release in mesenteric arteries from orchidectomized rats

Blanco-Rivero¹,

Sagredo²,

Balfagón³

et al. 2007

Journal of Endocrinology

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The aim of the present study was to assess the effect of endogenous male sex hormones on endothelial nitric oxide synthase (eNOS) expression, release and function of the endothelial nitric oxide (NO), as well as to assess the regulatory action of protein kinase C (PKC) on acetylcholine (ACh)-induced endothelial NO release. For this purpose, superior mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used. eNOS expression and basaland ACh-induced NO release were similar in arteries from both groups of rats. Orchidectomy decreased the vasodilator effect induced by ACh but did not alter that induced by sodium nitroprusside (SNP). The superoxide anion scavenger, superoxide dismutase (SOD), or the membrane-permeable mimetic of SOD, tempol, only enhanced ACh-induced relaxation in arteries from orchidectomized rats. ACh-induced TXA 2 formation was higher in arteries from orchidectomized than from control rats. Neither the PKC activator, phorbol 12,13-dibutyrate (PDBu), nor the non-selective PKC inhibitor, calphostin C, modified basal-or ACh-induced NO release in arteries from control rats. In arteries from orchidectomized rats, basal-and ACh-induced endothelial NO release were increased by PDBu but decreased by calphostin C. Both Gö 6976, a PKC inhibitor that is partially selective for conventional PKC isoforms, as well as PKCz pseudosubstrate inhibitor (PKCz-PI) decreased both basal-and ACh-induced NO release in arteries from orchidectomized rats. Neither PDBu nor calphostin C modified the vasodilator response induced by ACh in arteries from control rats. In segments from orchidectomized rats, PDBu enhanced the ACh-induced response, but this response was not modified by calphostin C, Gö6976 or PKCz-PI. The vasodilator response induced by SNP was not altered by the PKC activators or inhibitors in any artery from either group. These results show that endogenous male sex hormone deprivation does not affect the eNOS expression or the endothelial NO release induced by ACh, but does decrease the vasodilator action of ACh, by increasing NO metabolism and TXA 2 formation. In addition, PKC seems to modulate eNOS activity only in mesenteric arteries from orchidectomized rats, in which conventional and PKCz isoforms are involved in the positive regulation of eNOS.

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“…The cAMP-PKA pathway is coupled to ADM receptors in various types of cells (Kitamura et al, 1993;Shimekake et al, 1995), including neural cells (Xu and Krukoff, 2005). In addition, PKA mediates nNOS activation induced by diverse stimuli, such as electrical field stimulation (Ferrer et al, 2004) and application of endothelin (Jaureguiberry et al, 2004) or ␤-adrenoceptor agonists (Birder et al, 2002). We now show that ADM increases cAMP levels in hypothalamic neurons and that the cAMP-PKA pathway mediates the ADM-induced NO production, demonstrated by the blockade of NO responses in the presence of the PKA inhibitors H-89 and Rp-cAMP.…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullin Stimulates Nitric Oxide Production from Primary Rat Hypothalamic Neurons: Roles of Calcium and Phosphatases

Krukoff²

2007

Molecular Pharmacology

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Adrenomedullin (ADM) in the brain plays important roles in the maintenance of homeostasis. Although in vivo evidence has suggested that nitric oxide (NO) mediates ADM's effects in the brain, mechanisms for ADM stimulation of NO production in neurons have not been identified. In the present study, primary hypothalamic neurons were used to characterize ADM-induced NO production and to study the underlying mechanisms. Using Calcium Orange/4-amino-5-methylamino-2Ј,7Ј-difluorofluorescein fluorescence live cell imaging, we found that ADM (1 or 10 nM, 5 min) significantly elevated [Ca 2ϩ ] i and NO production in a concentration-dependent manner. Ca 2ϩ and NO responses induced by 10 nM ADM were abolished by pretreatment with 50 M 1,2-bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid-acetoxymethyl ester (BAPTA-AM), an intracellular Ca 2ϩ chelator, or protein kinase A (PKA) inhibitors 5 M N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) and 50 M Rp-cAMP. Furthermore, the ADM-induced NO production was significantly attenuated by a protein phosphatase 1/2A inhibitor, okadaic acid (OA; 0.1 M), or calcineurin inhibitors, tacrolimus (FK506) (1 M) and cyclosporin A (CsA; 0.1 M). Using Western blotting, we found that ADM significantly decreased phosphorylation of neuronal nitric-oxide synthase (nNOS) at serine 847. This dephosphorylation was inhibited by 0.1 M OA, 1 M FK506, 0.1 M CsA, or 5 M H-89, and attenuated by 50 M BAPTA-AM. These results suggest that, in hypothalamic neurons, ADM elevates [Ca 2ϩ ] i via PKA-associated mechanisms. The PKA/Ca 2ϩ cascade leads to protein phosphatase (PP) 1/PP2A-and calcineurin-mediated dephosphorylation of nNOS. We hypothesize that the Ca 2ϩ increase and nNOS dephosphorylation contribute to activation of nNOS and production of NO in hypothalamic neurons.

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Protein kinase A increases electrical stimulation-induced neuronal nitric oxide release in rat mesenteric artery

Cited by 19 publications

References 29 publications

Effect of low-intensity direct current on expression of vascular endothelial growth factor and nitric oxide in diabetic foot ulcers

Effect of low-intensity direct current on expression of vascular endothelial growth factor and nitric oxide in diabetic foot ulcers

Protein kinase C activation increases endothelial nitric oxide release in mesenteric arteries from orchidectomized rats

Adrenomedullin Stimulates Nitric Oxide Production from Primary Rat Hypothalamic Neurons: Roles of Calcium and Phosphatases

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