Differential coupling of the human P2Y(11) receptor to phospholipase C and adenylyl cyclase

Br J Pharmacol. 2001 Jan;132(1):318-26. doi: 10.1038/sj.bjp.0703788.


1. The human P2Y(11) (hP2Y(11)) receptor was stably expressed in two cell lines, 1321N1 human astrocytoma cells (1321N1-hP2Y(11)) and Chinese hamster ovary cells (CHO-hP2Y(11)), and its coupling to phospholipase C and adenylyl cyclase was assessed. 2. In 1321N1-hP2Y(11) cells, ATP promoted inositol phosphate (IP) accumulation with low microM potency (EC(50)=8.5+/-0.1 microM), whereas it was 15 fold less potent (130+/-10 microM) in evoking cyclic AMP production. 3. In CHO-hP2Y(11) cells, ATP promoted IP accumulation with slightly higher potency (EC(50)=3.6+/-1.3 microM) than in 1321N1-hP2Y(11) cells, but it was still 15 fold less potent in promoting cyclic AMP accumulation (EC(50)=62.4+/-15.6 microM) than for IP accumulation. Comparable differences in potencies for promoting the two second messenger responses were observed with other adenosine nucleotide analogues. 4. In 1321N1-hP2Y(11) and CHO-hP2Y(11) cells, down regulation of PKC by chronic treatment with phorbol ester decreased ATP-promoted cyclic AMP accumulation by 60--80% (P<0.001) with no change in its potency. Likewise, chelation of intracellular Ca(2+) decreased ATP-promoted cyclic AMP accumulation by approximately 45% in 1321N1-hP2Y(11) cells, whereas chelation had no effect on either the efficacy or potency of ATP in CHO-hP2Y(11) cells. 5. We conclude that coupling of hP2Y(11) receptors to adenylyl cyclase in these cell lines is much weaker than coupling to phospholipase C, and that activation of PKC and intracellular Ca(2+) mobilization as consequences of inositol lipid hydrolysis potentiates the capacity of ATP to increase cyclic AMP accumulation in both 1321N1-hP2Y(11) and CHO-hP2Y(11) cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine Nucleotides / pharmacology
  • Adenosine Triphosphate / pharmacology
  • Adenylyl Cyclases / metabolism*
  • Adenylyl Cyclases / physiology
  • Animals
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Cyclic AMP / biosynthesis
  • Enzyme Activation
  • Humans
  • Inositol Phosphates / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Polymerase Chain Reaction
  • Protein Kinase C / metabolism
  • Receptors, Dopamine D1 / biosynthesis
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2 / physiology
  • Second Messenger Systems / physiology
  • Tumor Cells, Cultured
  • Type C Phospholipases / metabolism*
  • Type C Phospholipases / physiology


  • Adenine Nucleotides
  • Inositol Phosphates
  • P2RY11 protein, human
  • Phosphodiesterase Inhibitors
  • Receptors, Dopamine D1
  • Receptors, Purinergic P2
  • Adenosine Triphosphate
  • Cyclic AMP
  • Protein Kinase C
  • Type C Phospholipases
  • Adenylyl Cyclases
  • Calcium