16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation

Carmen Gonzalez, Ana M. Corbacho, Jason P. Eiserich, Celina Garcia, Fernando Lopez-Barrera, Veronica Morales-Tlalpan, Alma Barajas-Espinosa, Mauricio Diaz-Muñoz, Rafael Rubio, Sue Hwa Lin, Gonzalo Martinez De La Escalera, Carmen Clapp

Research output: Contribution to journalArticle

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Abstract

Activation of endothelial nitric oxide synthase (eNOS) and subsequent nitric oxide production (NO) are events that mediate the effect of important angiogenic, vasopermeability, and vasorelaxation factors, including vascular endothelial growth factor (VEGF), bradykinin (BK), and acetylcholine (ACh). The N-terminal 16-kDa fragment of prolactin (16K-PRL) acts on endothelial cells to inhibit angiogenesis both in vivo and in vitro. Here, we show that 16K-PRL inhibits VEGF-induced eNOS activation in endothelial cells. Inhibition of eNOS activation may mediate the antiangiogenic properties of 16K-PRL, because the NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1,2-diolate (DET-ANONOate) prevented 16K-PRL from blocking the VEGF-induced proliferation of endothelial cells. In addition, 16K-PRL inhibited eNOS activation by BK and blocked the BK-evoked traasient increase in intracellular Ca2+ in endothelial cells. This finding suggests that 16K-PRL interferes with the mobilization of intracellular Ca2+, thereby inhibiting the Ca 2+-dependent activation of eNOS. Blockage of eNOS activation can lead to inhibition of vasodilation. Consistently, 16K-PRL inhibited BK-induced relaxation of coronary vessels in isolated perfused guinea pig hearts. Moreover, 16K-PRL inhibited eNOS activation induced by ACh, and this action resulted in the inhibition of both ACh-evoked relaxation of coronary vessels in isolated perfused rat hearts and ACh-induced, endothelium-dependent relaxation of rat aortic segments. In conclusion, 16K-PRL can block the Ca2+-mediated activation of eNOS by three different vasoactive substances, and this action results in the inhibition of both angiogenesis and vasorelaxation.

Original languageEnglish (US)
Pages (from-to)5714-5722
Number of pages9
JournalEndocrinology
Volume145
Issue number12
DOIs
StatePublished - Dec 2004

Fingerprint

Nitric Oxide Synthase Type III
Vasodilation
Prolactin
Endothelium
Calcium
Bradykinin
Acetylcholine
Endothelial Cells
Vascular Endothelial Growth Factor A
Coronary Vessels
DEET
Nitric Oxide Donors
Nitric Oxide
Guinea Pigs

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Gonzalez, C., Corbacho, A. M., Eiserich, J. P., Garcia, C., Lopez-Barrera, F., Morales-Tlalpan, V., ... Clapp, C. (2004). 16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation. Endocrinology, 145(12), 5714-5722. https://doi.org/10.1210/en.2004-0647

16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation. / Gonzalez, Carmen; Corbacho, Ana M.; Eiserich, Jason P.; Garcia, Celina; Lopez-Barrera, Fernando; Morales-Tlalpan, Veronica; Barajas-Espinosa, Alma; Diaz-Muñoz, Mauricio; Rubio, Rafael; Lin, Sue Hwa; Martinez De La Escalera, Gonzalo; Clapp, Carmen.

In: Endocrinology, Vol. 145, No. 12, 12.2004, p. 5714-5722.

Research output: Contribution to journalArticle

Gonzalez, C, Corbacho, AM, Eiserich, JP, Garcia, C, Lopez-Barrera, F, Morales-Tlalpan, V, Barajas-Espinosa, A, Diaz-Muñoz, M, Rubio, R, Lin, SH, Martinez De La Escalera, G & Clapp, C 2004, '16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation', Endocrinology, vol. 145, no. 12, pp. 5714-5722. https://doi.org/10.1210/en.2004-0647
Gonzalez, Carmen ; Corbacho, Ana M. ; Eiserich, Jason P. ; Garcia, Celina ; Lopez-Barrera, Fernando ; Morales-Tlalpan, Veronica ; Barajas-Espinosa, Alma ; Diaz-Muñoz, Mauricio ; Rubio, Rafael ; Lin, Sue Hwa ; Martinez De La Escalera, Gonzalo ; Clapp, Carmen. / 16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation. In: Endocrinology. 2004 ; Vol. 145, No. 12. pp. 5714-5722.
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abstract = "Activation of endothelial nitric oxide synthase (eNOS) and subsequent nitric oxide production (NO) are events that mediate the effect of important angiogenic, vasopermeability, and vasorelaxation factors, including vascular endothelial growth factor (VEGF), bradykinin (BK), and acetylcholine (ACh). The N-terminal 16-kDa fragment of prolactin (16K-PRL) acts on endothelial cells to inhibit angiogenesis both in vivo and in vitro. Here, we show that 16K-PRL inhibits VEGF-induced eNOS activation in endothelial cells. Inhibition of eNOS activation may mediate the antiangiogenic properties of 16K-PRL, because the NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1,2-diolate (DET-ANONOate) prevented 16K-PRL from blocking the VEGF-induced proliferation of endothelial cells. In addition, 16K-PRL inhibited eNOS activation by BK and blocked the BK-evoked traasient increase in intracellular Ca2+ in endothelial cells. This finding suggests that 16K-PRL interferes with the mobilization of intracellular Ca2+, thereby inhibiting the Ca 2+-dependent activation of eNOS. Blockage of eNOS activation can lead to inhibition of vasodilation. Consistently, 16K-PRL inhibited BK-induced relaxation of coronary vessels in isolated perfused guinea pig hearts. Moreover, 16K-PRL inhibited eNOS activation induced by ACh, and this action resulted in the inhibition of both ACh-evoked relaxation of coronary vessels in isolated perfused rat hearts and ACh-induced, endothelium-dependent relaxation of rat aortic segments. In conclusion, 16K-PRL can block the Ca2+-mediated activation of eNOS by three different vasoactive substances, and this action results in the inhibition of both angiogenesis and vasorelaxation.",
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T1 - 16K-prolactin inhibits activation of endothelial nitric oxide synthase, intracellular calcium mobilization, and endothelium-dependent vasorelaxation

AU - Gonzalez, Carmen

AU - Corbacho, Ana M.

AU - Eiserich, Jason P.

AU - Garcia, Celina

AU - Lopez-Barrera, Fernando

AU - Morales-Tlalpan, Veronica

AU - Barajas-Espinosa, Alma

AU - Diaz-Muñoz, Mauricio

AU - Rubio, Rafael

AU - Lin, Sue Hwa

AU - Martinez De La Escalera, Gonzalo

AU - Clapp, Carmen

PY - 2004/12

Y1 - 2004/12

N2 - Activation of endothelial nitric oxide synthase (eNOS) and subsequent nitric oxide production (NO) are events that mediate the effect of important angiogenic, vasopermeability, and vasorelaxation factors, including vascular endothelial growth factor (VEGF), bradykinin (BK), and acetylcholine (ACh). The N-terminal 16-kDa fragment of prolactin (16K-PRL) acts on endothelial cells to inhibit angiogenesis both in vivo and in vitro. Here, we show that 16K-PRL inhibits VEGF-induced eNOS activation in endothelial cells. Inhibition of eNOS activation may mediate the antiangiogenic properties of 16K-PRL, because the NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1,2-diolate (DET-ANONOate) prevented 16K-PRL from blocking the VEGF-induced proliferation of endothelial cells. In addition, 16K-PRL inhibited eNOS activation by BK and blocked the BK-evoked traasient increase in intracellular Ca2+ in endothelial cells. This finding suggests that 16K-PRL interferes with the mobilization of intracellular Ca2+, thereby inhibiting the Ca 2+-dependent activation of eNOS. Blockage of eNOS activation can lead to inhibition of vasodilation. Consistently, 16K-PRL inhibited BK-induced relaxation of coronary vessels in isolated perfused guinea pig hearts. Moreover, 16K-PRL inhibited eNOS activation induced by ACh, and this action resulted in the inhibition of both ACh-evoked relaxation of coronary vessels in isolated perfused rat hearts and ACh-induced, endothelium-dependent relaxation of rat aortic segments. In conclusion, 16K-PRL can block the Ca2+-mediated activation of eNOS by three different vasoactive substances, and this action results in the inhibition of both angiogenesis and vasorelaxation.

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