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Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells.

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Title: Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells.
Authors: Mahesh S. Joshi1 mjoshi20@yahoo.com, Bruce Ferguson Jr.1, Johnson, Fruzsina K.2, Johnson, Robert A.3, Parthasarathy, Sampath2 mjoshi20@yahoo.com, Lancaster Jr., Jack R.4
Source: Proceedings of the National Academy of Sciences of the United States of America. 6/12/2007, Vol. 104 Issue 24, p9982-9987. 6p. 5 Graphs.
Subjects: Nitric oxide, Arginine, Ligands (Biochemistry), Imidazolines, Adrenergic receptors, Nifedipine
Abstract: Arginine contains the guanidinium group and thus has structural similarity to ligands of imidazoline and α-2 adrenoceptors (α-2 AR). Therefore, we investigated the possibility that exogenous arginine may act as a ligand for these receptors in human umbilical vein endothelial cells and activate intracellular nitric oxide (NO) synthesis. Idazoxan, a mixed antagonist of imidazoline and α-2 adrenoceptors, partly inhibited ʟ-arginine-initiated NO formation as measured by a Griess reaction. Rauwolscine, a highly specific antagonist of α-2 AR, at very low concentrations completely inhibited NO formation. Like ʟ-arginine, agmatine (decarboxylated arginine) also activated NO synthesis, however, at much lower concentrations. We found that dexmedetomidine, a specific agonist of α-2 AR was very potent in activating cellular NO, thus indicating a possible role for α-2 AR in ʟ-arginine-mediated NO synthesis, o-arginine also activated NO production and could be inhibited by imidazoline and α-2 AR antagonists, thus indicating nonsubstrate actions of arginine. Pertussis toxin, an inhibitor of G proteins, attenuated ʟ-arginine-mediated NO synthesis, thus indicating mediation via G proteins. ʟ-type Ca2+ channel blocker nifedipine and phospholipase C inhibitor U73122 inhibited NO formation and thus implicated participation of a second messenger pathway. Finally, in isolated rat gracilis vessels, rauwolscine completely inhibited the ʟ-arginine-initiated vessel relaxation. Taken together, these data provide evidence for binding of arginine to membrane receptor(s), leading to the activation of endothelial NO synthase (eNOS) NO production through a second messenger pathway. These findings provide a previously unrecognized mechanistic explanation for the beneficial effects of ʟ-arginine in the cardiovascular system and thus provide new potential avenues for therapeutic development. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells.
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  Data: <searchLink fieldCode="AR" term="%22Mahesh+S%2E+Joshi%22">Mahesh S. Joshi</searchLink><relatesTo>1</relatesTo><i> mjoshi20@yahoo.com</i><br /><searchLink fieldCode="AR" term="%22Bruce+Ferguson+Jr%2E%22">Bruce Ferguson Jr.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Fruzsina+K%2E%22">Johnson, Fruzsina K.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Robert+A%2E%22">Johnson, Robert A.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Parthasarathy%2C+Sampath%22">Parthasarathy, Sampath</searchLink><relatesTo>2</relatesTo><i> mjoshi20@yahoo.com</i><br /><searchLink fieldCode="AR" term="%22Lancaster+Jr%2E%2C+Jack+R%2E%22">Lancaster Jr., Jack R.</searchLink><relatesTo>4</relatesTo>
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  Data: <searchLink fieldCode="DE" term="%22Nitric+oxide%22">Nitric oxide</searchLink><br /><searchLink fieldCode="DE" term="%22Arginine%22">Arginine</searchLink><br /><searchLink fieldCode="DE" term="%22Ligands+%28Biochemistry%29%22">Ligands (Biochemistry)</searchLink><br /><searchLink fieldCode="DE" term="%22Imidazolines%22">Imidazolines</searchLink><br /><searchLink fieldCode="DE" term="%22Adrenergic+receptors%22">Adrenergic receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Nifedipine%22">Nifedipine</searchLink>
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  Data: Arginine contains the guanidinium group and thus has structural similarity to ligands of imidazoline and α-2 adrenoceptors (α-2 AR). Therefore, we investigated the possibility that exogenous arginine may act as a ligand for these receptors in human umbilical vein endothelial cells and activate intracellular nitric oxide (NO) synthesis. Idazoxan, a mixed antagonist of imidazoline and α-2 adrenoceptors, partly inhibited ʟ-arginine-initiated NO formation as measured by a Griess reaction. Rauwolscine, a highly specific antagonist of α-2 AR, at very low concentrations completely inhibited NO formation. Like ʟ-arginine, agmatine (decarboxylated arginine) also activated NO synthesis, however, at much lower concentrations. We found that dexmedetomidine, a specific agonist of α-2 AR was very potent in activating cellular NO, thus indicating a possible role for α-2 AR in ʟ-arginine-mediated NO synthesis, o-arginine also activated NO production and could be inhibited by imidazoline and α-2 AR antagonists, thus indicating nonsubstrate actions of arginine. Pertussis toxin, an inhibitor of G proteins, attenuated ʟ-arginine-mediated NO synthesis, thus indicating mediation via G proteins. ʟ-type Ca2+ channel blocker nifedipine and phospholipase C inhibitor U73122 inhibited NO formation and thus implicated participation of a second messenger pathway. Finally, in isolated rat gracilis vessels, rauwolscine completely inhibited the ʟ-arginine-initiated vessel relaxation. Taken together, these data provide evidence for binding of arginine to membrane receptor(s), leading to the activation of endothelial NO synthase (eNOS) NO production through a second messenger pathway. These findings provide a previously unrecognized mechanistic explanation for the beneficial effects of ʟ-arginine in the cardiovascular system and thus provide new potential avenues for therapeutic development. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1073/pnas.0506824104
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      – Code: eng
        Text: English
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        StartPage: 9982
    Subjects:
      – SubjectFull: Nitric oxide
        Type: general
      – SubjectFull: Arginine
        Type: general
      – SubjectFull: Ligands (Biochemistry)
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      – SubjectFull: Imidazolines
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      – SubjectFull: Adrenergic receptors
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      – SubjectFull: Nifedipine
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      – TitleFull: Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells.
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              Text: 6/12/2007
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              Y: 2007
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