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Article: Increased ATP and ADO Overflow From Sympathetic Nerve Endings and Mesentery Endothelial Cells Plus Reduced Nitric Oxide Are Involved in Diabetic Neurovascular Dysfunction.

Donoso, M Verónica / Mascayano, M Jesús / Poblete, Inés M / Huidobro-Toro, J Pablo

2018 Volume 9, Page(s) 546

Abstract: Since the mechanism of human diabetic peripheral neuropathy and vascular disease in type 1 diabetes mellitus remains unknown, we assessed whether sympathetic transmitter overflow is altered by this disease and associated to vascular dysfunction. Diabetes ...

Abstract	Since the mechanism of human diabetic peripheral neuropathy and vascular disease in type 1 diabetes mellitus remains unknown, we assessed whether sympathetic transmitter overflow is altered by this disease and associated to vascular dysfunction. Diabetes was induced by streptozotocin (STZ)-treatment and compared to vehicle-treated rats. Aliquots of the
Language	English
Publishing date	2018-05-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2018.00546
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Article ; Online: Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation.

Lillo, Mauricio A / Gaete, Pablo S / Puebla, Mariela / Burboa, Pía C / Poblete, Inés / Figueroa, Xavier F

Oxidative medicine and cellular longevity

2021 Volume 2021, Page(s) 2678134

Abstract: Deletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane ... ...

Abstract	Deletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca
MeSH term(s)	Animals ; Arteries/drug effects ; Calcium Channels/metabolism ; Calcium Signaling ; Connexins/antagonists & inhibitors ; Connexins/metabolism ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Male ; Membrane Potentials/drug effects ; NADPH Oxidases/metabolism ; Nerve Tissue Proteins/antagonists & inhibitors ; Nerve Tissue Proteins/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Subcellular Fractions/metabolism ; Superoxides/metabolism ; Tetrodotoxin/pharmacology ; Vascular Resistance/drug effects ; Vasodilation/drug effects ; Rats
Chemical Substances	Calcium Channels ; Connexins ; Nerve Tissue Proteins ; pannexin 1, rat ; Superoxides (11062-77-4) ; Nitric Oxide (31C4KY9ESH) ; Tetrodotoxin (4368-28-9) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; NADPH Oxidases (EC 1.6.3.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2021-02-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2455981-7
ISSN	1942-0994 ; 1942-0994
ISSN (online)	1942-0994
ISSN	1942-0994
DOI	10.1155/2021/2678134
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Article ; Online: Critical contribution of Na

Lillo, Mauricio A / Gaete, Pablo S / Puebla, Mariela / Ardiles, Nicolás M / Poblete, Inés / Becerra, Alvaro / Simon, Felipe / Figueroa, Xavier F

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2018 Volume 32, Issue 4, Page(s) 2137–2147

Abstract: ... ...

Abstract	Na
MeSH term(s)	Animals ; Calcium/metabolism ; Cells, Cultured ; Endothelial Cells/metabolism ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Male ; Mesenteric Arteries/cytology ; Mesenteric Arteries/metabolism ; Mesenteric Arteries/physiology ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/physiology ; Myocytes, Smooth Muscle/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium-Calcium Exchanger/antagonists & inhibitors ; Sodium-Calcium Exchanger/metabolism ; Vasodilation
Chemical Substances	Sodium-Calcium Exchanger ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201700365RR
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Article ; Online: CGRP signalling inhibits NO production through pannexin-1 channel activation in endothelial cells.

Gaete, Pablo S / Lillo, Mauricio A / Puebla, Mariela / Poblete, Inés / Figueroa, Xavier F

Scientific reports

2019 Volume 9, Issue 1, Page(s) 7932

Abstract: Blood flow distribution relies on precise coordinated control of vasomotor tone of resistance arteries by complex signalling interactions between perivascular nerves and endothelial cells. Sympathetic nerves are vasoconstrictors, whereas endothelium- ... ...

Abstract	Blood flow distribution relies on precise coordinated control of vasomotor tone of resistance arteries by complex signalling interactions between perivascular nerves and endothelial cells. Sympathetic nerves are vasoconstrictors, whereas endothelium-dependent NO production provides a vasodilator component. In addition, resistance vessels are also innervated by sensory nerves, which are activated during inflammation and cause vasodilation by the release of calcitonin gene-related peptide (CGRP). Inflammation leads to superoxide anion (O
MeSH term(s)	Animals ; Calcitonin Gene-Related Peptide/metabolism ; Connexins/metabolism ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Inflammation/metabolism ; Inflammation/pathology ; Male ; Nerve Tissue Proteins/metabolism ; Nitric Oxide/metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; Superoxides/metabolism
Chemical Substances	Connexins ; Nerve Tissue Proteins ; pannexin 1, rat ; Superoxides (11062-77-4) ; Nitric Oxide (31C4KY9ESH) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
Language	English
Publishing date	2019-05-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-44333-w
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Article ; Online: Cross-cultural adaptation of four instruments to measure stigma towards people with mental illness and substance use problems among primary care professionals in Chile.

Parra Videla, Claudia / Sapag, Jaime C / Klabunde, Rachel / Velasco, Paola R / Anríquez, Samanta / Aracena Álvarez, Marcela / Mascayano, Franco / Bravo, Paulina / Sena, Brena F / Jofré Escalona, Ana / Bobbili, Sireesha J / Corrigan, Patrick W / Bustamante, Inés / Poblete, Fernando / Alvarado, Rubén

Transcultural psychiatry

2022 Volume 60, Issue 2, Page(s) 286–301

Abstract: Stigma toward people with mental illness and substance use problems is a significant global concern, and prevents people with these conditions from accessing treatment, particularly in primary health care (PHC) settings. Stigma is a cultural phenomenon ... ...

Abstract	Stigma toward people with mental illness and substance use problems is a significant global concern, and prevents people with these conditions from accessing treatment, particularly in primary health care (PHC) settings. Stigma is a cultural phenomenon that is influenced by particular contexts and can differ by country and region. The majority of stigma research focuses on Europe or North America leading to a lack of culturally relevant stigma research instruments for the Latin American context. The present study describes and discusses the methodology for cross-culturally adapting four stigma measurement scales to the Chilean context. The cross-cultural adaptation process included nine phases: (1) preparation; (2) independent translations; (3) synthesis 1 with expert committee; (4) focus groups and interviews with researchers, PHC professionals, and PHC users; (5) synthesis 2 with expert committee; (6) independent back translations; (7) synthesis 3 with expert committee; (8) pilot with PHC professionals; and (9) final revisions. The adaptation process included an array of diverse voices from the PHC context, and met three adaptation objectives defined prior to beginning the process (Understandability, Relevance, and Acceptability and Answer Options). The resulting, culturally adapted questionnaire is being validated and implemented within PHC settings across Chile to provide in-depth insight into stigma among PHC professionals in the country. The authors hope it will be useful for future research on mental illness and substance use stigma in similar settings across Latin America.
MeSH term(s)	Humans ; Chile ; Cross-Cultural Comparison ; Social Stigma ; Mental Disorders ; Substance-Related Disorders ; Primary Health Care
Language	English
Publishing date	2022-07-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1378978-8
ISSN	1461-7471 ; 1363-4615
ISSN (online)	1461-7471
ISSN	1363-4615
DOI	10.1177/13634615221100377
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Article ; Online: Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons.

Muñoz, Francisco J / Godoy, Juan A / Cerpa, Waldo / Poblete, Inés M / Huidobro-Toro, Juan Pablo / Inestrosa, Nibaldo C

Biochemical and biophysical research communications

2014 Volume 444, Issue 2, Page(s) 189–194

Abstract: Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production; however, Wnt-3a a ... ...

Abstract	Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist blocked the NO production. Wnt-5a activates the non-canonical Wnt/Ca(2+) signaling through a mechanism that depends on Ca(2+) release from Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into the neuronal cell surface. To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface.
MeSH term(s)	Animals ; Blotting, Western ; Calcium/metabolism ; Cell Membrane/metabolism ; Cells, Cultured ; HEK293 Cells ; Hippocampus/cytology ; Hippocampus/embryology ; Humans ; L Cells (Cell Line) ; Membrane Proteins/pharmacology ; Mice ; Models, Biological ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Nitric Oxide/metabolism ; Protein Transport/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Signal Transduction/drug effects ; Wnt Proteins/antagonists & inhibitors ; Wnt Proteins/metabolism ; Wnt Proteins/pharmacology ; Wnt-5a Protein
Chemical Substances	Membrane Proteins ; NR2B NMDA receptor ; Receptors, N-Methyl-D-Aspartate ; Sfrp2 protein, rat ; Wnt Proteins ; Wnt-5a Protein ; Wnt5a protein, rat ; Nitric Oxide (31C4KY9ESH) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2014-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2014.01.031
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Article: Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons

Muñoz, Francisco J / Godoy, Juan A / Cerpa, Waldo / Poblete, Inés M / Huidobro-Toro, Juan Pablo / Inestrosa, Nibaldo C

Biochemical and biophysical research communications. 2014 Feb. 07, v. 444

2014

Abstract	Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist blocked the NO production. Wnt-5a activates the non-canonical Wnt/Ca2+ signaling through a mechanism that depends on Ca2+ release from Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into the neuronal cell surface. To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface.
Keywords	antagonists ; calcium ; central nervous system ; neurons ; nitric oxide ; rats
Language	English
Dates of publication	2014-0207
Size	p. 189-194.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2014.01.031
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Article ; Online: UTP controls cell surface distribution and vasomotor activity of the human P2Y2 receptor through an epidermal growth factor receptor-transregulated mechanism.

Norambuena, Andrés / Palma, Francisco / Poblete, M Inés / Donoso, M Verónica / Pardo, Evelyn / González, Alfonso / Huidobro-Toro, J Pablo

The Journal of biological chemistry

2009 Volume 285, Issue 5, Page(s) 2940–2950

Abstract: Extracellular nucleotides transmit signals into the cells through the P2 family of cell surface receptors. These receptors are amply expressed in human blood vessels and participate in vascular tone control; however, their signaling mechanisms remain ... ...

Abstract	Extracellular nucleotides transmit signals into the cells through the P2 family of cell surface receptors. These receptors are amply expressed in human blood vessels and participate in vascular tone control; however, their signaling mechanisms remain unknown. Here we show that in smooth muscle cells of isolated human chorionic arteries, the activation of the P2Y(2) receptor (P2Y(2)R) induces not only its partition into membrane rafts but also its rapid internalization. Cholesterol depletion with methyl-beta-cyclodextrin reduced the association of the agonist-activated receptor into membrane rafts but did not affect either the UTP-mediated vasoconstrictions or the vasomotor responses elicited by both serotonin and KCl. Ex vivo perfusion of human chorionic artery segments with 1-10 mum UTP, a selective P2Y(2)R agonist, displaced the P2Y(2)R localization into membrane rafts within 1 min, a process preceded by the activation of both RhoA and Rac1 GTPases. AG1478, a selective and potent inhibitor of the epidermal growth factor receptor tyrosine kinase activity, not only blocked the UTP-induced vasomotor activity but also abrogated both RhoA and Rac1 activation, the P2Y(2)R association with membrane rafts, and its internalization. Altogether, these results show for the first time that the plasma membrane distribution of the P2Y(2)R is transregulated by the epidermal growth factor receptor, revealing an unsuspected functional interplay that controls both the membrane distribution and the vasomotor activity of the P2Y(2)R in intact human blood vessels.
MeSH term(s)	Actins/chemistry ; Arteries/metabolism ; Chorion/blood supply ; ErbB Receptors/metabolism ; Female ; Gene Expression Regulation ; Humans ; Ligands ; Membrane Microdomains/metabolism ; Placenta/metabolism ; Pregnancy ; Receptors, Purinergic P2/biosynthesis ; Receptors, Purinergic P2/chemistry ; Receptors, Purinergic P2Y2 ; Signal Transduction ; Uridine Triphosphate/chemistry ; Uridine Triphosphate/metabolism ; Vasomotor System/physiology
Chemical Substances	Actins ; Ligands ; P2RY2 protein, human ; Receptors, Purinergic P2 ; Receptors, Purinergic P2Y2 ; ErbB Receptors (EC 2.7.10.1) ; Uridine Triphosphate (UT0S826Z60)
Language	English
Publishing date	2009-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M109.081166
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Article: UTP Controls Cell Surface Distribution and Vasomotor Activity of the Human P2Y₂ Receptor through an Epidermal Growth Factor Receptor-transregulated Mechanism

Norambuena, Andrés / Palma, Francisco / Poblete, M. Inés / Donoso, M. Verónica / Pardo, Evelyn / González, Alfonso / Huidobro-Toro, J. Pablo

Journal of biological chemistry. 2010 Jan. 29, v. 285, no. 5

2010

Abstract	Extracellular nucleotides transmit signals into the cells through the P2 family of cell surface receptors. These receptors are amply expressed in human blood vessels and participate in vascular tone control; however, their signaling mechanisms remain unknown. Here we show that in smooth muscle cells of isolated human chorionic arteries, the activation of the P2Y₂ receptor (P2Y₂R) induces not only its partition into membrane rafts but also its rapid internalization. Cholesterol depletion with methyl-β-cyclodextrin reduced the association of the agonist-activated receptor into membrane rafts but did not affect either the UTP-mediated vasoconstrictions or the vasomotor responses elicited by both serotonin and KCl. Ex vivo perfusion of human chorionic artery segments with 1-10 μM UTP, a selective P2Y₂R agonist, displaced the P2Y₂R localization into membrane rafts within 1 min, a process preceded by the activation of both RhoA and Rac1 GTPases. AG1478, a selective and potent inhibitor of the epidermal growth factor receptor tyrosine kinase activity, not only blocked the UTP-induced vasomotor activity but also abrogated both RhoA and Rac1 activation, the P2Y₂R association with membrane rafts, and its internalization. Altogether, these results show for the first time that the plasma membrane distribution of the P2Y₂R is transregulated by the epidermal growth factor receptor, revealing an unsuspected functional interplay that controls both the membrane distribution and the vasomotor activity of the P2Y₂R in intact human blood vessels.
Language	English
Dates of publication	2010-0129
Size	p. 2940-2950.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Article: Anandamide elicits an acute release of nitric oxide through endothelial TRPV1 receptor activation in the rat arterial mesenteric bed.

Poblete, Inés M / Orliac, María Luz / Briones, René / Adler-Graschinsky, Edda / Huidobro-Toro, J Pablo

The Journal of physiology

2005 Volume 568, Issue Pt 2, Page(s) 539–551

Abstract: In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 +/- 9.2 pmol nitric oxide (NO) that was paralleled by a 2-fold increase in cGMP tissue ... ...

Abstract	In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 +/- 9.2 pmol nitric oxide (NO) that was paralleled by a 2-fold increase in cGMP tissue levels. The rise in NO released was mimicked by either (R)-(+)-methanandamide or the vanilloid receptor agonists resiniferatoxin and (E)-capsaicin but not by its inactive cis-isomer (Z)-capsaicin. The NO release elicited by either anandamide or capsaicin was reduced by the TRPV1 receptor antagonists 5'-iodoresiniferatoxin, SB 366791 and capsazepine as well as by the cannabinoid CB(1) receptor antagonists SR 141716A or AM251. The outflow of NO elicited by anandamide and capsaicin was also reduced by endothelium removal or NO synthase inhibition, suggesting the specific participation of endothelial TRPV1 receptors, rather than the novel endothelial TRPV4 receptors. Consistently, RT-PCR showed the expression of the mRNA coding for the rat TRPV1 receptor in the endothelial cell layer, in addition to its expression in sensory nerves. The participation of sensory nerves on the release of NO was precluded on the basis that neonatal denervation of the myenteric plexus sensory nerves did not modify the pattern of NO release induced by anandamide and capsaicin. We propose that low concentrations of anandamide, devoid of vasorelaxing effects, elicit an acute release of NO mediated predominantly by the activation of endothelial TRPV1 receptors whose physiological significance remains elusive.
MeSH term(s)	Anilides/pharmacology ; Animals ; Arachidonic Acids/pharmacology ; Cannabinoid Receptor Antagonists ; Capsaicin/analogs & derivatives ; Capsaicin/pharmacology ; Cinnamates/pharmacology ; Cyclic GMP/metabolism ; Diterpenes/pharmacology ; Dose-Response Relationship, Drug ; Endocannabinoids ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; In Vitro Techniques ; Male ; Mesenteric Artery, Superior/drug effects ; Mesenteric Artery, Superior/metabolism ; Nitric Oxide/metabolism ; Nitroarginine/pharmacology ; Perfusion ; Piperidines/pharmacology ; Polyunsaturated Alkamides ; Pyrazoles/pharmacology ; RNA, Messenger/analysis ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/drug effects ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism ; Vasodilation/drug effects
Chemical Substances	Anilides ; Arachidonic Acids ; Cannabinoid Receptor Antagonists ; Cinnamates ; Diterpenes ; Endocannabinoids ; N-(3-methoxyphenyl)-4-chlorocinnamanilide ; Piperidines ; Polyunsaturated Alkamides ; Pyrazoles ; RNA, Messenger ; TRPV Cation Channels ; Trpv2 protein, rat ; methanandamide (150314-39-9) ; Nitroarginine (2149-70-4) ; Nitric Oxide (31C4KY9ESH) ; resiniferatoxin (A5O6P1UL4I) ; Cyclic GMP (H2D2X058MU) ; capsazepine (LFW48MY844) ; rimonabant (RML78EN3XE) ; Capsaicin (S07O44R1ZM) ; anandamide (UR5G69TJKH)
Language	English
Publishing date	2005-10-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2005.094292
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