Dopamine D(1A) receptor regulation of phospholipase C isoform

Pei Ying Yu, Gilbert M. Eisner, Ikuyo Yamaguchi, Maral M. Mouradian, Robin A. Felder, Pedro A. Jose

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


In LTK- cells stably transfected with rat D(1A) 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-γ protein in a time-dependent manner. The latter was blocked by the D1 antagonist SKF83742 and by a D(1A) antisense oligodeoxynucleotide, indicating involvement of the D(1A) receptor. The fenoldopam-induced increase in PLC-γ and activity was mediated by protein kinase A (PKA) since it was blocked by the PKA antagonist R(p)-8-CTP-adenosine cyclic 3':5'- monophosphorothioate (R(p)-8-CTP-cAMP-S) and mimicked by direct stimulation of adenylyl cyclase with forskolin or by a PKA agonist, S(p)-cAMP-S. Protein kinase C (PKC) was also involved, since the fenoldopam-induced increase in PLC-γ 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, S(p)-8-CTP-cAMP-S, increased PKC activity, and direct stimulation of PKC with phorbol 12- myristate 13-acetate increased PLC-γ protein and activity, effects that were blocked by calphostin C. We suggest that the D(1A)-mediated stimulation of PLC occurs as a result of PKA activation. PKA then stimulates PLC-γ in cytosol and membrane via activation of PKC.

Original languageEnglish (US)
Pages (from-to)19503-19508
Number of pages6
JournalJournal of Biological Chemistry
Issue number32
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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