(+)-[^3H] Isradipine and [^3H] Glyburide Bindings to Heart and Lung Membranes From Rats With Monocrotaline-Induced Pulmonary Hypertension

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Author(s)

Abstract

We examined the binding of a 1, 4-dihydropyridine-sensitive Ca<SUP>2+</SUP> channel ligand, (+)-[<SUP>3</SUP>H]isradipine (PN200-110), and that of an ATP-sensitive K<SUP>+</SUP> (K<SUB>ATP</SUB>) channel ligand, [<SUP>3</SUP>H]glyburide, to heart, lung and brain membranes isolated from Sprague-Dawley rats made pulmonary hypertensive by monocrotaline, a pyrrolizidine alkaloid. A single subcutaneous injection of monocrotaline increased right ventricular systolic pressure, a measure of pulmonary arterial pressure, and the thickness of the right ventricular free wall in 3 to 4 weeks. The (+)-[<SUP>3</SUP>H]PN200-110 and [<SUP>3</SUP>H]glyburide binding site densities (B<SUB>max</SUB>) were reduced in hypertrophied right ventricles when normalized per unit protein in comparison with those of age-matched control (sham) rats, whereas the values of the dissociation constant (K<SUB>d</SUB>) of both ligands bound to the hypertrophied right ventricle were not significantly changed. The [<SUP>3</SUP>H]PN200-110 binding to the lung membranes of the monocrotaline-induced pulmonary hypertensive rats was increased. The results indicate that the change in the binding of 1, 4-dihydropyridine Ca<SUP>2+</SUP> and K<SUB>ATP</SUB> channel ligands to heart membranes may contribute to the pathological alteration of cardiopulmonary structure and functions in rats with pulmonary hypertension induced by monocrotaline.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 81(2), 176-184, 1999-10

    The Japanese Pharmacological Society

References:  27

Codes

  • NII Article ID (NAID)
    10008196807
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4886658
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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