(+)-[3H]isradipine and [3H]glyburide bindings to heart and lung membranes from rats with monocrotaline-induced pulmonary hypertension.
We examined the binding of a 1,4-dihydropyridine-sensitive Ca2+ channel ligand, (+)-[3H]isradipine (PN200-110), and that of an ATP-sensitive K+ (K(ATP)) 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 K(ATP) channel ligands to heart membranes may contribute to the pathological alteration of cardiopulmonary structure and functions in rats with pulmonary hypertension induced by monocrotaline.
Nakayama
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Japan.
Fukuta
Y
Y
Kiyoshi
A
A
Iwatsuki
Y
Y
Ishii
K
K
Ishikawa
T
T
Iida
M
M
Iwata
H
H
Enomoto
M
M
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000378:metabolism*; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000378:metabolism*; D066298:In Vitro Techniques; D017275:Isradipine / Q000378:metabolism*; D054086:KATP Channels; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D016686:Monocrotaline; D009206:Myocardium / Q000378:metabolism*; D011042:Poisons; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007004:Hypoglycemic Agents; D054086:KATP Channels; D011042:Poisons; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D016686:Monocrotaline; D005905:Glyburide; D017275:Isradipine