Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice

Autores
de la Torre, Eulalia; Davel, Lilia; Jasnis, María A.; Gotoh, Tomomi; Sacerdote de Lustig, Eugenia; Sales, María Elena
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Methods Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. Results TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because N ω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol significantly increased VEGF expression in TMps, and this effect was totally reversed by methoctramine and pirenzepine. Arginase and COX inhibitors partly decreased VEGF derived from TMps. Conclusion TMps themselves induce a potent angiogenic response that is augmented by carbachol action. mAchR activation triggers arginine metabolism, PGE2 synthesis and VEGF production, promoting neovascularization.
Fil: de la Torre, Eulalia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Davel, Lilia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Jasnis, María A.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Gotoh, Tomomi. Kumamoto University; Japón
Fil: Sacerdote de Lustig, Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sales, María Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Unidad documental simple
Materia
ADENOCARCINOMA
MACROPHAGES
SACERDOTE INVESTIGADORA
PUBLICACIONES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
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Consejo Nacional de Investigaciones Científicas y Técnicas
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing micede la Torre, EulaliaDavel, LiliaJasnis, María A.Gotoh, TomomiSacerdote de Lustig, EugeniaSales, María ElenaADENOCARCINOMAMACROPHAGESSACERDOTE INVESTIGADORAPUBLICACIONEShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Introduction The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Methods Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. Results TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because N ω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol significantly increased VEGF expression in TMps, and this effect was totally reversed by methoctramine and pirenzepine. Arginase and COX inhibitors partly decreased VEGF derived from TMps. Conclusion TMps themselves induce a potent angiogenic response that is augmented by carbachol action. mAchR activation triggers arginine metabolism, PGE2 synthesis and VEGF production, promoting neovascularization.Fil: de la Torre, Eulalia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Davel, Lilia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Jasnis, María A.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Gotoh, Tomomi. Kumamoto University; JapónFil: Sacerdote de Lustig, Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sales, María Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaUnidad documental simpleSpringer2006-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfnovalueArgentina[{ 'value':"",'auth':''}]Artículo científicoapplication/pdf-13de la Torre, Eulalia; Davel, Lilia; Jasnis, María A.; Gotoh, Tomomi; Sacerdote de Lustig, Eugenia; et al.; Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice; Springer; Breast Cancer Research; 7; 3; 8-2006; R345-R35215Alemania31Introduction The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Methods Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. Results TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because N ω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol significantly increased VEGF expression in TMps, and this effect was totally reversed by methoctramine and pirenzepine. Arginase and COX inhibitors partly decreased VEGF derived from TMps. Conclusion TMps themselves induce a potent angiogenic response that is augmented by carbachol action. mAchR activation triggers arginine metabolism, PGE2 synthesis and VEGF production, promoting neovascularization.810273/submit/conicet/edit-metadata.jspOtroSpringerGuardar y salirhttps://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1005https://doi.org/10.1186/bcr1005accepted-1acceptedR345-R352novalueMuscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing miceinfo:eu-repo/semantics/reference/url/139371Berlín2006ADENOCARCINOMAMACROPHAGESSACERDOTE INVESTIGADORAPUBLICACIONESUnidad documental simpleinfo:eu-repo/semantics/altIdentifier/url/eng[{ 'value':"de la Torre, Eulalia",'auth':'21244','org': [ {'value':'Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"','auth':'1393','pais':'Argentina','pais_id':'1'}]},{ 'value':"Davel, Lilia",'auth':'','org': [ {'value':'Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"','auth':'1393','pais':'Argentina','pais_id':'1'}]},{ 'value':"Jasnis, María A.",'auth':'','org': [ {'value':'Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"','auth':'1393','pais':'Argentina','pais_id':'1'}]},{ 'value':"Gotoh, Tomomi",'auth':'','org': [ {'value':"Kumamoto University",'auth':'','pais':'Japón','pais_id':'64'}]},{ 'value':"Sacerdote de Lustig, Eugenia",'auth':'3','org': [ {'value':'Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"','auth':'1393','pais':'Argentina','pais_id':'1'},{'value':"Consejo Nacional de Investigaciones Científicas y Técnicas",'auth':'2565','pais':'Argentina','pais_id':'1'}]},{ 'value':"Sales, María Elena",'auth':'','org': [ {'value':'Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"','auth':'1393','pais':'Argentina','pais_id':'1'}]}]info:eu-repo/semantics/altIdentifier/url/info:eu-repo/semantics/altIdentifier/doi/1465-542X1Breast Cancer Researchacceptedd4721328-1166-4ac4-829d-c85ec68a5dd1EscalaGrisc866c4ce-f1b5-4a9b-9914-b7bfaa2589e3600No especificaUniversidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"1141No especificaapplication/pdfhttp://hdl.handle.net/11336/122690de la Torre, Eulalia; Davel, Lilia; Jasnis, María A.; Gotoh, Tomomi; Sacerdote de Lustig, Eugenia; et al.; Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice; Springer; Breast Cancer Research; 7; 3; 8-2006; R345-R3521465-542Xenginfo:eu-repo/semantics/altIdentifier/url/https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1005info:eu-repo/semantics/altIdentifier/doi/10.1186/bcr1005info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:01:19Zoai:ri.conicet.gov.ar:11336/122690instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:01:19.908CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
title Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
spellingShingle Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
de la Torre, Eulalia
ADENOCARCINOMA
MACROPHAGES
SACERDOTE INVESTIGADORA
PUBLICACIONES
title_short Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
title_full Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
title_fullStr Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
title_full_unstemmed Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
title_sort Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
dc.creator.none.fl_str_mv de la Torre, Eulalia
Davel, Lilia
Jasnis, María A.
Gotoh, Tomomi
Sacerdote de Lustig, Eugenia
Sales, María Elena
author de la Torre, Eulalia
author_facet de la Torre, Eulalia
Davel, Lilia
Jasnis, María A.
Gotoh, Tomomi
Sacerdote de Lustig, Eugenia
Sales, María Elena
author_role author
author2 Davel, Lilia
Jasnis, María A.
Gotoh, Tomomi
Sacerdote de Lustig, Eugenia
Sales, María Elena
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ADENOCARCINOMA
MACROPHAGES
SACERDOTE INVESTIGADORA
PUBLICACIONES
topic ADENOCARCINOMA
MACROPHAGES
SACERDOTE INVESTIGADORA
PUBLICACIONES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Methods Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. Results TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because N ω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol significantly increased VEGF expression in TMps, and this effect was totally reversed by methoctramine and pirenzepine. Arginase and COX inhibitors partly decreased VEGF derived from TMps. Conclusion TMps themselves induce a potent angiogenic response that is augmented by carbachol action. mAchR activation triggers arginine metabolism, PGE2 synthesis and VEGF production, promoting neovascularization.
Fil: de la Torre, Eulalia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Davel, Lilia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Jasnis, María A.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Gotoh, Tomomi. Kumamoto University; Japón
Fil: Sacerdote de Lustig, Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sales, María Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Unidad documental simple
description Introduction The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Methods Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. Results TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because N ω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol significantly increased VEGF expression in TMps, and this effect was totally reversed by methoctramine and pirenzepine. Arginase and COX inhibitors partly decreased VEGF derived from TMps. Conclusion TMps themselves induce a potent angiogenic response that is augmented by carbachol action. mAchR activation triggers arginine metabolism, PGE2 synthesis and VEGF production, promoting neovascularization.
publishDate 2006
dc.date.none.fl_str_mv 2006-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/122690
de la Torre, Eulalia; Davel, Lilia; Jasnis, María A.; Gotoh, Tomomi; Sacerdote de Lustig, Eugenia; et al.; Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice; Springer; Breast Cancer Research; 7; 3; 8-2006; R345-R352
1465-542X
url http://hdl.handle.net/11336/122690
identifier_str_mv de la Torre, Eulalia; Davel, Lilia; Jasnis, María A.; Gotoh, Tomomi; Sacerdote de Lustig, Eugenia; et al.; Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice; Springer; Breast Cancer Research; 7; 3; 8-2006; R345-R352
1465-542X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1005
info:eu-repo/semantics/altIdentifier/doi/10.1186/bcr1005
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
novalue
Argentina
[{ 'value':"",'auth':''}]
Artículo científico
application/pdf
-1
3
de la Torre, Eulalia; Davel, Lilia; Jasnis, María A.; Gotoh, Tomomi; Sacerdote de Lustig, Eugenia; et al.; Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice; Springer; Breast Cancer Research; 7; 3; 8-2006; R345-R352
15
Alemania
31
Introduction The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Methods Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. Results TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because N ω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol significantly increased VEGF expression in TMps, and this effect was totally reversed by methoctramine and pirenzepine. Arginase and COX inhibitors partly decreased VEGF derived from TMps. Conclusion TMps themselves induce a potent angiogenic response that is augmented by carbachol action. mAchR activation triggers arginine metabolism, PGE2 synthesis and VEGF production, promoting neovascularization.
8
10273
/submit/conicet/edit-metadata.jsp
Otro
Springer
Guardar y salir
https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1005
https://doi.org/10.1186/bcr1005
accepted
-1
accepted
R345-R352
novalue
Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice
info:eu-repo/semantics/reference/url/
1393
7
1
Berlín
2006
ADENOCARCINOMA
MACROPHAGES
SACERDOTE INVESTIGADORA
PUBLICACIONES
Unidad documental simple
info:eu-repo/semantics/altIdentifier/url/
eng
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info:eu-repo/semantics/altIdentifier/url/
info:eu-repo/semantics/altIdentifier/doi/
1465-542X
1
Breast Cancer Research
accepted
d4721328-1166-4ac4-829d-c85ec68a5dd1
EscalaGris
c866c4ce-f1b5-4a9b-9914-b7bfaa2589e3
600
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No especifica
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dc.publisher.none.fl_str_mv Springer
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repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
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