Enhanced expression of Ca2+ channel alpha1A and beta4 subunits and phosphorylated tyrosine hydroxylase in the adrenal gland of N-type Ca2+ channel alpha1B subunit-deficient mice with a CBA/JN genetic background.
Electrophysiologic studies have demonstrated that adrenal medulla chromaffin cells express voltage-dependent P/Q-, N-, L-, and R-type Ca2+ channels and that these channels regulate release of norepinephrine and epinephrine. However, N-type Ca2+ channel alpha1B-deficient mice with a CBA/JN background show normal plasma norepinephrine and epinephrine levels, presumably owing to compensation by other gene(s). To examine the expression patterns of the P/Q-type alpha1A, L-type alpha1C/alpha1D, and R-type alpha1E, beta1, beta2, beta3, and beta4 subunits, as well as of tyrosine hydroxylase (Th), dopamine beta hydroxylase (Dbh), and phenylethanolamine-N-methyltransferase (Pnmt) in the adrenal gland of alpha1B-deficient mice, we used real-time quantitative reverse transcription-polymerase chain reaction and Western blot analyses. The expression levels of alpha1A, beta4, Th, and Th phosphorylated at serine 40 were higher in homozygous mice than in wild-type and heterozygous mice, but the expression levels of alpha1C, alpha1D, alpha1E, beta1, beta2, beta3, Dbh, and Pnmt did not differ among wild-type, heterozygous, and homozygous mice. These results suggest that the compensatory mechanisms to maintain normal levels of epinephrine and norepinephrine in the adrenal gland of N-type Ca2+ channel alpha1B-deficient mice include increased expression of alpha1A and beta4 subunits and increased catecholamine biosynthetic activity.
Takahashi
Eiki
E
Tsukuba Research Laboratory, Eisai Co. Ltd., Tsukuba, Ibaraki 300-2635, Japan. e2-takahashi@hhc.eisai.co.jp
Nagasu
Takeshi
T
D000311:Adrenal Glands / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type / Q000235:genetics* / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000235:genetics* / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005260:Female; D015870:Gene Expression; D005838:Genotype; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D023421:Models, Animal; D009638:Norepinephrine / Q000097:blood; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D004837:Epinephrine; D009638:Norepinephrine; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; C492923:Cacnb1 protein, mouse