Molecular cloning and characterization of the platelet-activating factor receptor gene expressed in the human heart

T Sugimoto1, H Tsuchimochi, C G McGregor

  • 1Department of Internal Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905.

Insights

Researchers identified a cardiac Platelet-Activating Factor (PAF) receptor in human heart tissue. This finding suggests a novel mechanism for regulating PAF receptor expression in the heart.

Area of Science:

  • Cardiovascular Biology
  • Molecular Pharmacology
  • Receptor Biology

Background:

  • Platelet-Activating Factor (PAF) is known to reduce cardiac contractility and blood pressure.
  • Understanding the cardiac PAF receptor is crucial for elucidating PAF's cardiovascular effects.

Purpose of the Study:

  • To identify and characterize the PAF receptor in human ventricular tissue.
  • To investigate potential tissue-specific regulation of PAF receptor expression.

Main Methods:

  • Screening of a human ventricular cDNA library using a probe for the guinea pig lung PAF receptor.
  • Functional expression studies in Xenopus oocytes to assess PAF-induced currents.
  • Northern blot analysis of human cardiac tissues to determine mRNA size.

Main Results:

  • Four cDNA clones (HV1-4) were isolated; HV3 and HV4 encoded the human leukocyte PAF receptor.
  • PAF stimulation of Xenopus oocytes expressing HV3 or HV4 cRNA induced Ca(2+)-activated Cl- currents.
  • Northern blotting revealed a ~4 kb mRNA band in human ventricles and atria, suggesting a specific transcript size.

Conclusions:

  • A cardiac PAF receptor, identical to the leukocyte receptor polypeptide, was identified.
  • Differences in the 5' untranslated region of HV3/4 compared to the leukocyte receptor suggest regulatory mechanisms.
  • Results indicate a potential tissue-specific translational regulation of cardiac PAF receptor mRNA expression.

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