1994 Fiscal Year Final Research Report Summary
Establishment of model cell lines for analyzing relation of angiotensin II-caused diseases with long term potentiation
| Project/Area Number |
05660384
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MIYAZAKI Hitoshi Univ.of Tsukuba, Inst.of Appl.Biochem., Associated Prof., 応用生物化学系, 助教授 (40183636)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Angiotensin II Receptor / AtT20 / ACTH / Phospholipase C / Calcium Channel / Adenylate Cyclase |
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| Research Abstract |
1.We have established an AtT20 cell line stably expressing the recombinant human angiotensin II (Ang II) receptor type 1 (AT1) to provide a model for analyzing the relation of Ang II-caused diseases with long term potentiation. AtT20 cells are derived from mouse anterior pituitary cells secreting adrenocorticotropin (ACTH). Following finding were obtained concerning characteristics of this cell line, which are essential for the purpose of this study.
(1) In these transfected cells, Ang II induced activation of phospholipase C and voltage-dependent calcium channel, and inhibition of adenylate cyclase activity through the AT1 receptor. Among these the former two pathways were found to relate with Ang II-induced ACTH secretion.
(2) This cell line was found to be a good model for elucidating the cross-talk between Ang II and corticotropin releasing factor (CRF) signalling pathways, because Ang II had a synergistic effect with CRF,whose functions are mediated by cAMP,on ACTH secretion.
2.We tried to develop a microperfusion system to investigate whether Ang II induces a phenomenon in these endocrine cells corresponding to long term potentiation observed in neural cells. Unfortunately, reliable results were not obtained in this system since high levels of basal ACTH secretion prevented us from selectively detecting the amount of Ang II-induced ACTH secretion. We are now looking for optimal conditions in which the long term potentiation is observed using the cells cultured in dishes but not those filled in micropipette in the microperfusion system.
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