Linked Life Data

6255882

Source:http://linkedlifedata.com/resource/pubmed/id/6255882

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1981-2-24
pubmed:abstractText
We previously demonstrated that chlorpromazine (CPZ), 7,8 diOH-CPZ and 3,7,8 triOH-CPZ were potent inhibitors of central adenylate cyclase systems. The present studies were thus designed to observe whether further substitutions of dihydroxy groups on the CPZ molecule would influence adenylate cyclase in broken cell preparations of the rat frontal cortex. The inhibition of adenylate cyclase by 7,8 diOH-CPZ was further found to be noncompetitive with respect to ATP concentration. Raising the Ca++ concentration obliterated adenylate cyclase activation by either dopamine or 5'-guanylylimidodiphosphate (Gpp(NH)p) alone or in combination, while inhibition by 7,8 diOH-CPZ was overcome. The enzyme inhibition by 7,8 diOH-CPZ was not influenced, however, by increasing Mg++ concentration. Incubation of rat cortical homogenates with CPZ, 3,7,8 triOH-CPZ or 6,9 diOH-CPZ inhibited stimulation of adenylate cyclase activity while either 3,7- or 3,8 diOH-CPZ resulted in an enhancement of enzyme activity. In further study, using the high speed cortical supernatant, the high Km form of cyclic AMP phosphodiesterase and its activation by the Ca++-dependent, heat stable regulator protein were inhibited by CPZ, 6,9 dioxo-, 7,8 dioxo-, 3,7diOH-, 3,8 diOH-, 6,9 diOH-, 7,9 diOH- and 7,8 diOH-CPZs, but not by 3,7,8 triOH-CZP. The high affinity-low Km form of the enzyme was inhibited to a considerably lesser extent by these analogs. The studies reveal rather diverse and complicated actions of CPZ and its putative metabolites on central enzyme systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0301-4533
pubmed:author
pubmed:issnType
Print
pubmed:volume
247
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-70
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1980
pubmed:articleTitle
Di- and trihydroxy analogs of chlorpromazine influence the central activity of adenylate cyclase and cyclic AMP phosphodiesterase.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't