|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
8
|
|
pubmed:dateCreated |
2005-3-29
|
|
pubmed:abstractText |
Adenylate cyclase (EC 4.6.1.1) type 9 (AC9) activity has been shown to be inhibited by PMA activation of novel protein kinase C (nPKC) isoforms. In the current study the effect on AC9 activity of activating PKC in physiological relevant manner was examined. Contrary to the anticipated inhibitory effect of activating PKCs through Gq-coupled receptors, activation of transiently expressed Gq-coupled serotonin 5-HT2A or muscarinic M5 receptors resulted in the potentiation of isoproterenol-stimulated cyclic AMP accumulation in HEK293 cells stably expressing AC9 (HEK-AC9). Consistent with Gq-mediated activation of PKC, the addition of the PKC inhibitor bisindolylmaleimide further potentiated isoproterenol-stimulated cyclic AMP accumulation. Expression of a constitutively active mutant of Galphaq in HEK-AC9 cells also produced an enhancement in basal and isoproterenol-stimulated cyclic AMP accumulation. We also examined the role of Galphaq-mediated release of intracellular Ca2+ on the observed potentiation of AC9 activity, by depleting intracellular Ca2+ stores with thapsigargin. In Ca2+-depleted HEK-AC9 cells, activation of transiently expressed M5 receptors resulted in inhibition of isoproterenol-stimulated cyclic AMP accumulation that was blocked by bisindolylmaleimide, indicating that M5 potentiation of AC9 activity requires Ca2+. This prompted us to examine the effects of the calmodulin antagonist W7 and the Ca2+/calmodulin-dependent kinase II (CaMK II) inhibitor KN-93. Pretreating cells with W7 and KN-93 significantly inhibited M5-mediated potentiation of isoproterenol-stimulated cyclic AMP accumulation in HEK-AC9 cells, suggesting that Galphaq potentiation of AC9 activity involves Ca2+/calmodulin and CaMK II. This data provides evidence for Ca2+-mediated potentiation of AC9 activity.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Benzylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/KN 93,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT2,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/W 7,
http://linkedlifedata.com/resource/pubmed/chemical/adenylate cyclase 9,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
0006-2952
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
69
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1247-56
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:15794946-Adenylate Cyclase,
pubmed-meshheading:15794946-Benzylamines,
pubmed-meshheading:15794946-Calcium,
pubmed-meshheading:15794946-Calmodulin,
pubmed-meshheading:15794946-Cell Line,
pubmed-meshheading:15794946-Cyclic AMP,
pubmed-meshheading:15794946-Enzyme Activation,
pubmed-meshheading:15794946-Enzyme Inhibitors,
pubmed-meshheading:15794946-GTP-Binding Protein alpha Subunits, Gq-G11,
pubmed-meshheading:15794946-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:15794946-Humans,
pubmed-meshheading:15794946-Indoles,
pubmed-meshheading:15794946-Isoproterenol,
pubmed-meshheading:15794946-Maleimides,
pubmed-meshheading:15794946-Mutation,
pubmed-meshheading:15794946-Protein Kinase C,
pubmed-meshheading:15794946-Receptors, Muscarinic,
pubmed-meshheading:15794946-Receptors, Serotonin, 5-HT2,
pubmed-meshheading:15794946-Signal Transduction,
pubmed-meshheading:15794946-Sulfonamides,
pubmed-meshheading:15794946-Thapsigargin
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Galphaq potentiation of adenylate cyclase type 9 activity through a Ca2+/calmodulin-dependent pathway.
|
|
pubmed:affiliation |
Purdue University, Department of Medicinal Chemistry and Molecular Pharmacology, 575 Stadium Mall Drive, West Lafayette, IN 47907-2051, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
