ION CHANNELS, RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM
ION CHANNELS, RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM
批准号:
6161943
负责人:
J W DALY
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
受体激动剂和各种毒素调节离子通道和
英文摘要
Receptors agonists and various toxins serve to modulate ion channels and
generation of second messengers, including cyclic nucleotides, inositol
phosphates diacylglycerides, arachidonic acid prostaglandins,
sphingosine, and phosphatidic acid. Calcium, sodium, potassium, and
magnesium ions after translocation through ion channels or by transport
proteins can cause activation of release processes, contractile
proteins, adenylate and guanylate cyclase, phosphodiesterases, protein
kinases, phospholipases, ATPases and other enzymes. Modulatory
interactions or "cross-talk" occurs both between the second messenger
systems and the ion transport systems. Maitotoxin-from a marine
dinoflagellate activates unique, calcium channels, which do not appear
to be identical to any know calcium-channel, including the so-called
calcium release-activated calcium (CRAC) channel. However, both
maitotoxin and CRAC channels are effectively blocked by certain
imidazoles (SKF 96365, miconazole, clotrimazole). Both channels are
also blocked by trifluoperazine, but there are many other agents that
block only the maitotoxin-activated channel. Loperamide is one of the
most potent blockers of maitotoxin-elicited channels, but causes an
apparent enhancement of calcium influx through the CRAC-channels that
have been opened as a result of receptor-, thapsigargin-, or
ionomycin-elicited depletion of IP3-sensitive intracellular pools of
calcium in a variety of cell types. The effect of loperamide is unique,
highly dependent on structure, and not readily reversed by imidazoles.
Loperamide does not have any effect on levels of intracellular calcium
if CRAC channels have not been activated. Loperamide does not augment
sphingosine-elicited influx of calcium. Thus, loperamide does not
augment sphingosine-elicited influx of calcium nor does augment influx
of calcium through L-type calcium channels. The imidazoles, in addition
to blocking CRAC channels, cause both release and influx of calcium in
HL60 cells. Calmidazolium causes the greatest influx, but simpler
analogs of calmidazolium have no effect. Erythrina alkaloids cause both
competitive and noncompetitive blockade of nicotinic channels.
Erysovine is the most potent member of these alkaloids at the central
neuronal nicotinic receptor-channel. Tropane analogs of epiboxidine had
nanomolar affinities for central nicotinic receptor-channels.
Remarkably an N-benzyl derivative retained agonist activity. From a
series of tropanes related in structure to a Chinese herbal alkaloid
baogongteng A, the analog 6beta-acetoxytropane proved to be a potent
muscarinic agonist with some selectivity towards M2-receptors. Other
analogs appeared to be selective towards M1-receptors and, therefore,
may have potential in decreasing cognitive deficits.
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ION CHANNELS, RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM
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批准号:2572985
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ADENOSINE RECEPTOR AGONISTS AND ANTAGONISTS
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批准号:5201962
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:3940629
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ION CHANNELS--RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM
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批准号:3875849
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ION CHANNELS, RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM
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批准号:3776290
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:3875848
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:3964464
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ION CHANNELS, RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM
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批准号:3754183
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:3917733
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ADENOSINE RECEPTOR AGONISTS AND ANTAGONISTS
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批准号:3875853
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
CYCLIC NUCLEOTIDES AND OTHER SECOND MESSENGERS IN THE NERVOUS SYSTEM
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批准号:3940631
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
CYCLIC NUCLEOTIDES AND OTHER SECOND MESSENGERS IN THE NERVOUS SYSTEM
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批准号:3964466
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:5201957
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ADENOSINE RECEPTOR AGONISTS AND ANTAGONISTS
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批准号:2572988
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:2572984
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ADENOSINE RECEPTOR AGONISTS AND ANTAGONISTS
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批准号:3754186
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:3776288
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:3839843
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
ADENOSINE RECEPTOR AGONISTS AND ANTAGONISTS
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批准号:3839849
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES
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批准号:6161942
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:J W DALY
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依托单位:
海外基金