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Dopamine D1A receptor regulation of phospholipase C isoform.

Authors: Yu, PY  Eisner, GM  Yamaguchi, I  Mouradian, MM  Felder, RA  Jose, PA 
Citation: Yu PY, etal., J Biol Chem. 1996 Aug 9;271(32):19503-8.
Pubmed: (View Article at PubMed) PMID:8702641

In LTK- cells stably transfected with rat D1A receptor cDNA, fenoldopam, a D1 agonist, increased phosphatidylinositol 4, 5-bisphosphate hydrolysis in a time-dependent manner. In the cytosol, phospholipase C (PLC) activity increased (50 +/- 7%) in 30 s, returned to basal level at 4 h, and decreased below basal values by 24 h; in the membrane, PLC activity also increased (36 +/- 13%) in 30 s, returned to basal level at 10 min, and decreased below basal value at 4 and 24 h. Fenoldopam also increased PLC-gamma protein in a time-dependent manner. The latter was blocked by the D1 antagonist SKF83742 and by a D1A antisense oligodeoxynucleotide, indicating involvement of the D1A receptor. The fenoldopam-induced increase in PLC-gamma and activity was mediated by protein kinase A (PKA) since it was blocked by the PKA antagonist Rp-8-CTP-adenosine cyclic 3':5'-monophosphorothioate (Rp-8-CTP-cAMP-S) and mimicked by direct stimulation of adenylyl cyclase with forskolin or by a PKA agonist, Sp-cAMP-S. Protein kinase C (PKC) was also involved, since the fenoldopam-induced increase in PLC-gamma protein was blocked by two different PKC inhibitors, calphostin C and chelerythrine; calphostin C also blocked the fenoldopam-induced increase in PLC activity. In addition, forskolin and a PKA agonist, Sp-8-CTP-cAMP-S, increased PKC activity, and direct stimulation of PKC with phorbol 12-myristate 13-acetate increased PLC-gamma protein and activity, effects that were blocked by calphostin C. We suggest that the D1A-mediated stimulation of PLC occurs as a result of PKA activation. PKA then stimulates PLC-gamma in cytosol and membrane via activation of PKC.

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CRRD Object Information
CRRD ID: 8553617
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.