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Differential synthesis of ACh in the carotid body between DBA/2J and A/J strains of mice
Author(s) -
Shirahata Machiko,
Lee Soo,
Balbir Alexander,
Okumura Mariko
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a785
Subject(s) - vesicular acetylcholine transporter , choline acetyltransferase , acetylcholine , carotid body , cholinergic , endocrinology , medicine , gene knockdown , biology , stimulation , glomus cell , synaptic vesicle , messenger rna , microbiology and biotechnology , chemistry , vesicle , biochemistry , gene , membrane
Hypoxic stimulation of the carotid body (CB) induces a wide range of systemic responses. Variability of these responses among individuals suggests genetic regulation of CB function. Among several inbred strains of mice, DBA/2J mice show more robust hypoxic responses than A/J mice. We have hypothesized that the differences of hypoxic responses between these strains of mice are partly due to differential expression of cholinergic pathways in the CB. Many studies have shown that ACh and ATP are major excitatory neurotransmitters in the CB. Increased release of ACh during hypoxia has been observed in the CB of the cat, rabbit, and swine. Choline acetyltransferase (an ACh synthesizing enzyme; ChAT) and vesicular ACh transporter (VAChT) by which ACh is transported to synaptic vesicles are localized in glomus cells of the cat, rat, and swine. Measuring ACh from the mouse CB is not technically realistic. Thus, in this study, we compare mRNA expression for ChAT and VAChT in the CB between DBA/2J and A/J mice. In DBA/2J mice, mRNAs for ChAT and VAChT were expressed at comparable levels to the cerebral cortex (relative to β‐actin). However, in A/J mice neither mRNAs were detected. Immunohistochemistry showed that VAChT was localized in glomus cells of DBA/2J mice. The results suggest that ACh synthesis and storage are severely compromised in A/J mice, resulting low hypoxic responses. Supported by AHA0255358N, HL 72293, HL50712.