Presynaptic modulation of the norepinephrine-induced β-adrenergic receptor desensitization phenomenon in vivo

I. Nakamura, T. Yoshikawa, T. Anzai, A. Baba, M. Iwata, Yumiko Wainai, M. Suzuki, S. Ogawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: In vivo administration of norepinephrine fails to cause β-adrenergic receptor desensitization. However, short-term exposure of cultured cells to norepinephrine induces the phenomenon in vitro. We sought to identify the local regulatory mechanisms responsible for in vivo β-adrenergic receptor desensitization in congestive heart failure. Methods and Results: Control rabbits received norepinephrine (n = 7) or saline (n = 7) for 1 week, and rabbits with chemical denervation induced by 6-hydroxydopamine also received norepinephrine (n = 7) or saline (n = 7). Myocardial norepinephrine content decreased 80% in both groups of denervated rabbits. β1-Adrenergic receptor density in denervated rabbits receiving norepinephrine was lower than in those receiving saline but not in control rabbits receiving norepinephrine. Isoproterenol-competition assay revealed that there was a lower number of high-affinity binding sites with loss of guanosine triphosphate shift in denervated rabbits receiving norepinephrine. Isoproterenol-stimulated adenylyl cyclase activity in control rabbits receiving norepinephrine was lower than in those receiving saline. In denervated rabbits receiving norepinephrine, forskolin-stimulated adenylyl cyclase activity was also reduced. Immunoreactive G-protein coupled receptor kinase-2 level was increased in denervated rabbits receiving norepinephrine. Conclusion: There are profound alterations in β-adrenergic receptor signaling after exposure to norepinephrine in the denervated heart. Defects in neuronal uptake may play a pivotal role in β-adrenergic receptor desensitization in vivo.

Original languageEnglish
Pages (from-to)350-358
Number of pages9
JournalJournal of Cardiac Failure
Volume6
Issue number4
DOIs
Publication statusPublished - 2000

Fingerprint

Adrenergic Receptors
Norepinephrine
Rabbits
Isoproterenol
Adenylyl Cyclases
G-Protein-Coupled Receptor Kinase 2
Oxidopamine
Denervation
Colforsin
Guanosine Triphosphate
Cultured Cells
Heart Failure
Binding Sites

Keywords

  • Adenylyl cyclase
  • Denervation
  • G-protein coupled receptor kinase
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Presynaptic modulation of the norepinephrine-induced β-adrenergic receptor desensitization phenomenon in vivo. / Nakamura, I.; Yoshikawa, T.; Anzai, T.; Baba, A.; Iwata, M.; Wainai, Yumiko; Suzuki, M.; Ogawa, S.

In: Journal of Cardiac Failure, Vol. 6, No. 4, 2000, p. 350-358.

Research output: Contribution to journalArticle

Nakamura, I. ; Yoshikawa, T. ; Anzai, T. ; Baba, A. ; Iwata, M. ; Wainai, Yumiko ; Suzuki, M. ; Ogawa, S. / Presynaptic modulation of the norepinephrine-induced β-adrenergic receptor desensitization phenomenon in vivo. In: Journal of Cardiac Failure. 2000 ; Vol. 6, No. 4. pp. 350-358.
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AU - Nakamura, I.

AU - Yoshikawa, T.

AU - Anzai, T.

AU - Baba, A.

AU - Iwata, M.

AU - Wainai, Yumiko

AU - Suzuki, M.

AU - Ogawa, S.

PY - 2000

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N2 - Background: In vivo administration of norepinephrine fails to cause β-adrenergic receptor desensitization. However, short-term exposure of cultured cells to norepinephrine induces the phenomenon in vitro. We sought to identify the local regulatory mechanisms responsible for in vivo β-adrenergic receptor desensitization in congestive heart failure. Methods and Results: Control rabbits received norepinephrine (n = 7) or saline (n = 7) for 1 week, and rabbits with chemical denervation induced by 6-hydroxydopamine also received norepinephrine (n = 7) or saline (n = 7). Myocardial norepinephrine content decreased 80% in both groups of denervated rabbits. β1-Adrenergic receptor density in denervated rabbits receiving norepinephrine was lower than in those receiving saline but not in control rabbits receiving norepinephrine. Isoproterenol-competition assay revealed that there was a lower number of high-affinity binding sites with loss of guanosine triphosphate shift in denervated rabbits receiving norepinephrine. Isoproterenol-stimulated adenylyl cyclase activity in control rabbits receiving norepinephrine was lower than in those receiving saline. In denervated rabbits receiving norepinephrine, forskolin-stimulated adenylyl cyclase activity was also reduced. Immunoreactive G-protein coupled receptor kinase-2 level was increased in denervated rabbits receiving norepinephrine. Conclusion: There are profound alterations in β-adrenergic receptor signaling after exposure to norepinephrine in the denervated heart. Defects in neuronal uptake may play a pivotal role in β-adrenergic receptor desensitization in vivo.

AB - Background: In vivo administration of norepinephrine fails to cause β-adrenergic receptor desensitization. However, short-term exposure of cultured cells to norepinephrine induces the phenomenon in vitro. We sought to identify the local regulatory mechanisms responsible for in vivo β-adrenergic receptor desensitization in congestive heart failure. Methods and Results: Control rabbits received norepinephrine (n = 7) or saline (n = 7) for 1 week, and rabbits with chemical denervation induced by 6-hydroxydopamine also received norepinephrine (n = 7) or saline (n = 7). Myocardial norepinephrine content decreased 80% in both groups of denervated rabbits. β1-Adrenergic receptor density in denervated rabbits receiving norepinephrine was lower than in those receiving saline but not in control rabbits receiving norepinephrine. Isoproterenol-competition assay revealed that there was a lower number of high-affinity binding sites with loss of guanosine triphosphate shift in denervated rabbits receiving norepinephrine. Isoproterenol-stimulated adenylyl cyclase activity in control rabbits receiving norepinephrine was lower than in those receiving saline. In denervated rabbits receiving norepinephrine, forskolin-stimulated adenylyl cyclase activity was also reduced. Immunoreactive G-protein coupled receptor kinase-2 level was increased in denervated rabbits receiving norepinephrine. Conclusion: There are profound alterations in β-adrenergic receptor signaling after exposure to norepinephrine in the denervated heart. Defects in neuronal uptake may play a pivotal role in β-adrenergic receptor desensitization in vivo.

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