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

The Japanese Journal of Pharmacology

Koichi Nakayama²  Mari Iida¹  Tomohisa Ishikawa²  Akihiko Kiyoshi²  Yoshiyuki Iwatsuki²  Kunio Ishii²  Makoto Enomoto¹  Hijiri Iwata¹  Yoshihisa Fukuta² 

[1] Biosafety Research Center, Foods, Drugs and Pesticides;Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka

关键词: Ca2+ channel;    ATP-sensitive K+ channel;    Monocrotaline;    Pulmonary hypertension;    Binding assay;   

DOI  :  10.1254/jjp.81.176

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(27)Cited-By(2)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.

【 授权许可】

Unknown