pubmed-article:15794946 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:15794946 | lifeskim:mentions | umls-concept:C0332307 | lld:lifeskim |
pubmed-article:15794946 | lifeskim:mentions | umls-concept:C0001492 | lld:lifeskim |
pubmed-article:15794946 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
pubmed-article:15794946 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
pubmed-article:15794946 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
pubmed-article:15794946 | lifeskim:mentions | umls-concept:C0279023 | lld:lifeskim |
pubmed-article:15794946 | lifeskim:mentions | umls-concept:C0596235 | lld:lifeskim |
pubmed-article:15794946 | pubmed:issue | 8 | lld:pubmed |
pubmed-article:15794946 | pubmed:dateCreated | 2005-3-29 | lld:pubmed |
pubmed-article:15794946 | 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. | lld:pubmed |
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pubmed-article:15794946 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15794946 | pubmed:language | eng | lld:pubmed |
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pubmed-article:15794946 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:15794946 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:15794946 | pubmed:month | Apr | lld:pubmed |
pubmed-article:15794946 | pubmed:issn | 0006-2952 | lld:pubmed |
pubmed-article:15794946 | pubmed:author | pubmed-author:WattsVal JVJ | lld:pubmed |
pubmed-article:15794946 | pubmed:author | pubmed-author:CumbayMedhane... | lld:pubmed |
pubmed-article:15794946 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:15794946 | pubmed:day | 15 | lld:pubmed |
pubmed-article:15794946 | pubmed:volume | 69 | lld:pubmed |
pubmed-article:15794946 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:15794946 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:15794946 | pubmed:pagination | 1247-56 | lld:pubmed |
pubmed-article:15794946 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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pubmed-article:15794946 | pubmed:year | 2005 | lld:pubmed |
pubmed-article:15794946 | pubmed:articleTitle | Galphaq potentiation of adenylate cyclase type 9 activity through a Ca2+/calmodulin-dependent pathway. | lld:pubmed |
pubmed-article:15794946 | pubmed:affiliation | Purdue University, Department of Medicinal Chemistry and Molecular Pharmacology, 575 Stadium Mall Drive, West Lafayette, IN 47907-2051, USA. | lld:pubmed |
pubmed-article:15794946 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:15794946 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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