Jpn. J. Pharmacol. 81 (2), 176-184 (1999)

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

Koichi Nakayama1, Yoshihisa Fukuta1, Akihiko Kiyoshi1, Yoshiyuki Iwatsuki1, Kunio Ishii1, Tomohisa Ishikawa1, Mari Iida2, Hijiri Iwata2 and Makoto Enomoto2

1Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka,
52 - 1 Yada, Shizuoka City, Shizuoka 422 - 8526, Japan
2Biosafety Research Center, Foods, Drugs and Pesticides, 582 - 2 Arahama, Shioshinden, Fukude, Iwata, Shizuoka 437 - 1312, Japan

Abstract: We examined the binding of a 1,4-dihydropyridine-sensitive Ca2+ channel ligand, (+)[3H]isradipine (PN200-110), and that of an ATP-sensitive K+ (KATP) channel ligand, [3H]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 (+)-[3H]PN200-110 and [3H]glyburide binding site densities (Bmax) 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 (Kd) of both ligands bound to the hypertrophied right ventricle were not significantly changed. The [3H]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 Ca2+ and KATP channel ligands to heart membranes may contribute to the pathological alteration of cardiopulmonary structure and functions in rats with pulmonary hypertension induced by monocrotaline.

Keywords: Ca2+ channel, ATP-sensitive K+ channel, Monocrotaline, Pulmonary hypertension, Binding assay

Copyrightę The Japanese Pharmacological Society 1999

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