CELL MEMBRANE ACTIVITY IN FUNCTIONAL PSYCHOSES
CELL MEMBRANE ACTIVITY IN FUNCTIONAL PSYCHOSES
批准号:
3374979
负责人:
MABEL R HOKIN
金额:
$12.26万
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-08-15 至 1990-03-31
关键词:
adenosinetriphosphatase cell membrane erythrocyte membrane human subject lithium membrane permeability mental disorder chemotherapy mental disorder diagnosis ouabain phosphatidylcholines phosphatidylethanolamines phosphatidylinositols phosphatidylserines psychobiology psychopharmacology radiotracer schizophrenia
中文摘要
总体目标是研究膜NAK-ATPase活性和内源
哇巴因样调节因子在双相情感障碍中的研究
锂治疗对肌醇磷脂代谢的影响。
主要目的是确定是否存在NAK-ATPase的变体
这是双相情感障碍所特有的。放射性
将开发光亲和标签,它将标记阿尔法和
红细胞膜和身体中酶的β亚基
脑组织。将开发分离标记的方法
酶亚基和选择性降解产物。这些将被用来
确定该酶的变种形式是否可以在
双相情感障碍。如果成功,将尝试
根据这些发现,开发一种针对这种疾病的诊断测试。
第二个目标是调查是否存在不正常的监管
双相患者内源性哇巴因样因子对NAK-ATPase活性的影响
情感障碍。抑制NAK-ATPase活性和置换的因素
哇巴因结合将从动物的大脑和其他组织中分离出来。
这些将与来自双相和正常的红细胞NAK-ATPase进行测试
受试者要确定在亲和力或广度上是否有任何差异
具有抑制活性。亲和力或易感性的可能变化
在锂治疗期间,这些因素的抑制将随之而来。
将建立循环中哇巴因样物的检测方法
血浆提取物中的抑制因子。循环中的水平
抑制因子将在正常和双相受试者中进行测量,并且
在锂治疗期间。
第三个目标是确定膜的响应性
锂治疗过程中磷脂酰肌醇信号系统的变化。回应
其中涉及磷脂酰肌醇的信号系统将在
接受锂治疗的患者的血小板并与
锂治疗前和正常对照组的反应。的水平
肌醇、肌醇磷酸盐、肌醇磷脂和其他脂类
从患者的淋巴细胞、血小板和红细胞中检测
锂治疗,并将与正常对照组的水平进行比较。
英文摘要
Overall objectives are to study membrane NaK-ATPase activity and endogenous
ouabain-like regulatory factors in bipolar affective disorder, and to study
the effects of lithium therapy on phosphoinositide metabolism.
A major aim is to determine whether there is a variant of the NaK-ATPase
which is specific for bipolar affective disorder. Radioactive
photoaffinity labels will be developed which will label both the alpha and
beta subunits of the enzyme in erythrocyte membranes and in post mortem
brain tissue. Methods will be developed for the separation of the labeled
enzyme subunits and selective degradation products. These will be used to
determine whether a variant form of the enzyme can be demonstrated in
bipolar affective disorder. If successful, an attempt will be made to
develop a diagnostic test for the disorder, based on these findings.
A second aim is to investigate whether there may be abnormal regulation of
NaK-ATPase activity by an endogenous ouabain-like factor in bipolar
affective disorder. Factors which inhibit NaK-ATPase activity and displace
ouabain-binding will be isolated from animal brain and other tissues.
These will be tested against erythrocyte NaK-ATPase from bipolar and normal
subjects to determine whether there is any difference in affinity or extend
of inhibitory activity. Possible changes in affinity or susceptibility to
inhibition by these factors during lithium therapy will be followed.
Methodology will be developed for the assay of circulating ouabain-like
inhibitory factor in extracts of blood plasma. Circulating levels of
inhibitory factor will be measured in normal and bipolar subjects, and
during lithium therapy.
A third aim is to determine whether the responsivity of the membrane
phosphoinositide signal system changes during lithium therapy. Responses
which involve the phophoinositide signal system will be measured in
platelets from patients receiving lithium therapy and compared with
responses before lithium therapy and in normal controls. The levels of
inosito, inositol phosphates, phosphoinositides and other lipids will be
measured in lymphocytes, platelets and erythrocytes from patients receiving
lithium therapy and will be compared with the levels in normal controls.
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Photoaffinity labeling of (Na+K+)-ATPase with [125I]iodoazidocymarin.
用[125I]碘叠氮西马林对 (Na K )-ATP 酶进行光亲和标记。
DOI:
--
发表时间:
1984
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
[Lowndes,JM, Hokin-Neaverson,M, Ruoho,AE]
通讯作者:
Ruoho,AE
Lithium-induced accumulation of inositol 1-phosphate during cholecystokinin octapeptide- and acetylcholine-stimulated phosphatidylinositol breakdown in dispersed mouse pancreas acinar cells.
在分散的小鼠胰腺腺泡细胞中,胆囊收缩素八肽和乙酰胆碱刺激的磷脂酰肌醇分解期间,锂诱导肌醇 1-磷酸的积累。
DOI:
--
发表时间:
1984
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
[Hokin-Neaverson,M, Sadeghian,K]
通讯作者:
Sadeghian,K
Kinetics of phosphorylation of Na+/K(+)-ATPase by protein kinase C.
蛋白激酶 C 磷酸化 Na /K( )-ATPase 的动力学。
DOI:
10.1016/0167-4889(90)90069-p
发表时间:
1990
期刊:
Biochimica et biophysica acta
影响因子:
--
作者:
[Lowndes,JM, Hokin-Neaverson,M, Bertics,PJ]
通讯作者:
Bertics,PJ
N-(3-(p-azido-m-[125I]iodophenyl)propionyl)-succinimide--a heterobifunctional reagent for the synthesis of radioactive photoaffinity ligands: synthesis of a carrier-free 125I-labeled cardiac glycoside photoaffinity label.
N-(3-(对叠氮基-间-[125I]碘苯基)丙酰基)-琥珀酰亚胺--一种用于合成放射性光亲和配体的异双功能试剂:合成无载体的125I标记的强心苷光亲和标记。
DOI:
10.1016/0003-2697(88)90007-3
发表时间:
1988
期刊:
Analytical biochemistry
影响因子:
2.9
作者:
[Lowndes,JM, Hokin-Neaverson,M, Ruoho,AE]
通讯作者:
Ruoho,AE
Identification of a third form of Na,K-ATPase catalytic subunit in rat brain by photoaffinity labeling.
通过光亲和标记鉴定大鼠脑中 Na,K-ATP 酶催化亚基的第三种形式。
DOI:
--
发表时间:
1988
期刊:
Progress in clinical and biological research
影响因子:
--
作者:
[Lowndes,JM, Ruoho,AE, Hokin-Neaverson,M]
通讯作者:
Hokin-Neaverson,M
共 8 条
SMALL INSTRUMENTATION PROGRAM
-
批准号:3526098
-
项目类别:
-
资助金额:$8.34万
-
财政年份:1988
-
负责人:MABEL R HOKIN
-
依托单位:
CONTROLLED TEMPERATURE SHAKER-INCUBATOR & OTHER ITEMS
-
批准号:3524608
-
项目类别:
-
资助金额:$8.0万
-
财政年份:1987
-
负责人:MABEL R HOKIN
-
依托单位:
CELL MEMBRANE ACTIVITY IN FUNCTIONAL PSYCHOSES
-
批准号:3374975
-
项目类别:
-
资助金额:$11.07万
-
财政年份:1985
-
负责人:MABEL R HOKIN
-
依托单位:
CELL MEMBRANE ACTIVITY IN FUNCTIONAL PSYCHOSES
-
批准号:3374978
-
项目类别:
-
资助金额:$11.39万
-
财政年份:1985
-
负责人:MABEL R HOKIN
-
依托单位:
CONTROL OF MEMBRANE ACTIVITY BY NEUROTRANSMITTERS
-
批准号:3395368
-
项目类别:
-
资助金额:$13.81万
-
财政年份:1977
-
负责人:MABEL R HOKIN
-
依托单位:
CONTROL OF MEMBRANE ACTIVITY BY NEUROTRANSMITTERS
-
批准号:3395367
-
项目类别:
-
资助金额:$14.81万
-
财政年份:1977
-
负责人:MABEL R HOKIN
-
依托单位:
CONTROL OF MEMBRANE ACTIVITY BY NEUROTRANSMITTERS
-
批准号:3395369
-
项目类别:
-
资助金额:$15.15万
-
财政年份:1977
-
负责人:MABEL R HOKIN
-
依托单位:
CONTROL OF MEMBRANE ACTIVITY BY NEUROTRANSMITTERS
-
批准号:3395362
-
项目类别:
-
资助金额:$13.45万
-
财政年份:1977
-
负责人:MABEL R HOKIN
-
依托单位:
CONTROL OF MEMBRANE ACTIVITY BY NEUROTRANSMITTERS
-
批准号:3395370
-
项目类别:
-
资助金额:$15.17万
-
财政年份:1977
-
负责人:MABEL R HOKIN
-
依托单位:
海外基金