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March 1, 1996Hypertension

Regulation of Angiotensin II Type 2 Receptor Gene by the Protein Kinase C–Calcium Pathway

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Population

Rat PC12 cells and myocytes isolated from neonatal rat heart

Comparison

Exposure to cycloheximide, serum deprivation… vs Proliferating cells or untreated control cells

Design

Preclinical

Authors

KKKazuhisa KijimaKansai Medical UniversityHMHiroaki MatsubaraUniversity of Notre DameSMSatoshi MurasawaTufts University

Discussion

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Implication

Hypothesis-generating for AT2 regulation in vascular cells; leaves open translation to human hypertension therapies.

Key Points

  • To examine how cellular growth arrest and the protein kinase C–calcium signaling pathway regulate angiotensin II type 2 (AT2) receptor gene transcription and mRNA stability.
  • Assessed AT2 receptor mRNA expression and transcription rates in proliferating, confluent, and serum-deprived rat PC12 cells treated with cycloheximide, TPA, or the calcium ionophore A23187.
  • Examined the effects of TPA, A23187, and vasoactive agents (norepinephrine and angiotensin II) on AT2 receptor mRNA regulation in isolated neonatal rat cardiac myocytes.
  • AT2 receptor expression increased during growth arrest via elevated gene transcription and required de novo protein synthesis, as evidenced by cycloheximide-mediated inhibition.
  • Activation of protein kinase C by TPA decreased both gene transcription and mRNA stability, whereas calcium mobilization by A23187 selectively reduced mRNA stability in PC12 cells and cardiac myocytes.
  • Vasoactive factors coupled to the protein kinase C–calcium cascade, including norepinephrine and angiotensin II, downregulated AT2 receptor mRNA levels in neonatal cardiac myocytes.

Structured PICO

P
Population
Rat PC12 cells and myocytes isolated from neonatal rat heart
I
Intervention
Exposure to cycloheximide, serum deprivation, 12-O-tetradecanoylphorbol 13-acetate (TPA), calcium ionophore A23187, norepinephrine, or angiotensin II
C
Comparator
Proliferating cells or untreated control cells
O
Outcome
Angiotensin II type 2 (AT2) receptor expression (mRNA levels and gene transcription rate)surrogate

The protein kinase C-calcium pathway downregulates AT2 receptor expression, providing a mechanism by which vasoactive substances and neurotransmitters may modulate cellular responsiveness to angiotensin II.

Cite This Study

Kijima et al. (1996) studied this question.

synapsesocial.com/papers/6a7162ebac440176ef2a1068https://doi.org/10.1161/01.hyp.27.3.529
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1The Growth-dependent Expression of Angiotensin II Type 2 Receptor Is Regulated by Transcription Factors Interferon Regulatory Factor-1 and −21995 · 65 citations
  2. 2A G Protein Is Involved in the Angiotensin AT2 Receptor Inhibition of the T-Type Calcium Current in Non-differentiated NG108-15 Cells1995 · 122 citations
  3. 3Angiotensin II Receptor: Molecular Cloning, Functions, and Regulation.1994 · 54 citations
  4. 4Regulatory elements that mediate expression of the gene for the angiotensin II type 1a receptor for the rat.1993 · 55 citations
  5. 5Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype.1993 · 1,429 citations