Journal
LIFE SCIENCES
Volume 91, Issue 21-22, Pages 981-985Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2012.04.031
Keywords
Acetylcholine; Choline acetyltransferase; cAMP; Mediatophore; Phorbol ester; Protein kinase C
Funding
- Grants-in-Aid for Scientific Research [23590121] Funding Source: KAKEN
Ask authors/readers for more resources
Aims: Muscarinic and nicotinic acetylcholine (ACh) receptors are expressed in immune cells. ACh synthesized by choline acetyltransferase (ChAT) and released in T cells binds to these receptors. Furthermore, we have recently demonstrated the involvement of mediatophore, a homooligomer of a 16-kDa proteolipid subunit of vacuolar H+-ATPase, in ACh release from T cells. In this study, we investigated the effects of phorbol 12-myristate 13-acetate (PMA), dibutyryl cAMP (dbcAMP) and FK506, an immunosuppressant calcineurin inhibitor, on lymphocytic cholinergic activity in T cells. Main methods: We determined the content and release of ACh in human leukemic T cell line MOLT-3 cells using a sensitive and specific radioimmunoassay for ACh. In addition, expression of ChAT mRNA and ChAT activity were investigated using reverse-transcription-polymerase chain reaction and Fonnum method, respectively. Key findings: Phytohemagglutinin (PHA), a T-cell activator, up-regulated ChAT mRNA expression, synthesis and release of ACh. PMA, a protein kinase C (PKC) activator, and dbcAMP, a protein kinase A (PKA) activator, also increased ChAT activity and ACh synthesis by up-regulating ChAT gene expression. FK506 inhibited PHA-induced up-regulation of ChAT mRNA expression, suggesting the involvement of calcineurin-mediated pathways in ChAT gene transcription. Significance: Activation of PKC and PICA up-regulates ACh synthesis in T cells, and immunological activation triggers ChAT gene transcription through calcineurin-mediated pathways. (C) 2012 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available