Identification of 1,4-dihydropyridine binding domains within the primary structure of the alpha 1 subunit of the skeletal muscle L-type calcium channel.
Calcium channel blockers are drugs that bind to the alpha 1 subunit of L-type calcium channels and selectively inhibit ion movements through these channels. Determination of the mechanism of channel blockade requires localization of drug-binding sites within the primary structure of the receptor. In this study the 1,4-dihydropyridine-binding site of the membrane bound receptor has been identified. The covalently labeled receptor was purified and digested with trypsin. The labeled peptide fragments were immunoprecipitated with sequence-directed antibodies. The data indicate the existence of at least three distinct dihydropyridine-binding domains within the primary structure of the alpha 1 subunit.
Kalasz
H
H
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267.
Watanabe
T
T
Yabana
H
H
Itagaki
K
K
Naito
K
K
Nakayama
H
H
Schwartz
A
A
Vaghy
P L
PL
D000345:Affinity Labels; D000818:Animals; D001386:Azides / Q000737:chemistry; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines / Q000737:chemistry / Q000378:metabolism*; D009124:Muscle Proteins / Q000032:analysis*; D009132:Muscles / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010777:Photochemistry; D011817:Rabbits; D014316:Tritium
D000345:Affinity Labels; D001386:Azides; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D009124:Muscle Proteins; D010446:Peptide Fragments; D014316:Tritium; C041130:azidopine; C038806:1,4-dihydropyridine