Cloning of the Cav 1.3 (alpha1D) L-type Ca2+ channel from mouse and its expression in the liver.
Dihydropyridine (DHP) type Ca2+ channel blocker (CCB) is effective in treatment of hepatitis in man. L-type Ca2+ channel is a target of DHP-CCB, and basic studies suggest that L-type Ca2+ channel alpha1D-subunit (Cav 1.3) seems to be a target of drug development for the treatment of hepatitis. Mouse hepatitis model is useful to study the effect of DHP-CCB on hepatitis. In order to use mouse hepatitis model to screen DHP-CCB specific for Cav 1.3, Cav 1.3 expressed in the mouse liver should have enough structural homology with that of human Cav 1.3. cDNA of the Cav 1.3 was cloned from mouse brain by reverse transcription polymerase chain reaction. The primary structure of the mouse Cav 1.3 comprises an open reading frame of 6540 bp encoding 2180 amino acids. Liver transcript lacked 60 and 45 bases from 1497 to 1556, and from 3949 to 3993 of the sequence, respectively, due to results of an alternative splicing. The present results indicated that mouse Cav 1.3 exhibited 96% homology with human Cav 1.3 and was expressed in the liver. Thus, mouse hepatitis model seemed to be useful to screen DHP-CCB specific for Cav 1.3.
Okamoto
Toshihiro
T
Research Laboratories, Nippon Chemiphar Co., Ltd., Saitama 341-0005, Japan.
Kobayashi
Toshiyuki
T
Hino
Okio
O
D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D012313:RNA / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction
C485995:Cacna1d protein, mouse; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D018076:DNA, Complementary; D004095:Dihydropyridines; C093712:Cacna1d protein, rat; D012313:RNA; C038806:1,4-dihydropyridine