Dual effects of protein kinase-C on receptor-stimulated cAMP accumulation in a human T-cell leukemia line

Eur J Pharmacol. 1989 Mar 7;172(1):51-60. doi: 10.1016/0922-4106(89)90044-8.


In the human T-cell leukemia line Jurkat, cAMP accumulation stimulated by the adenosine receptor agonist 5'-N-ethylcarboxamido adenosine (NECA) was enhanced by tumour-promoting phorbol esters whereas the prostaglandin receptor-stimulated accumulation of cAMP was antagonized. Phorbol esters did not alter the adenosine or prostaglandin receptor-stimulated accumulation of cAMP in cells in which the phospholipid/Ca2+-dependent protein kinase (protein kinase-C) was down-regulated. cAMP stimulation induced by cholera toxin (CT) was enhanced by phorbol esters by 100-300%. The cAMP production induced by forskolin was never enhanced by more than 50% by 4 beta-phorbol-12,13-dibutyrate (PDBu) and there was no stimulation at all after down-regulation of the adenosine receptor by treatment with NECA. Phorbol ester enhanced the NECA-stimulated accumulation of cAMP, even in the presence of concentrations of forskolin that increased the cAMP accumulation several-fold. From these data we conclude that protein kinase-C can interact with receptors coupled to adenylate cyclase in a stimulatory as well as an inhibitory manner. Moreover, protein kinase-C appears to interact with signal transduction at two levels, one highly receptor-specific and one distal to the receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Adenosine-5'-(N-ethylcarboxamide)
  • Adenylyl Cyclases / metabolism
  • Blotting, Western
  • Cell Line
  • Cholera Toxin / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Dinoprostone / pharmacology
  • Humans
  • Leukemia, T-Cell / metabolism*
  • Phorbol Esters / pharmacology
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Receptors, Prostaglandin / metabolism
  • Receptors, Purinergic / metabolism*


  • Phorbol Esters
  • Receptors, Prostaglandin
  • Receptors, Purinergic
  • Colforsin
  • Adenosine-5'-(N-ethylcarboxamide)
  • Cholera Toxin
  • Cyclic AMP
  • Protein Kinase C
  • Adenylyl Cyclases
  • Adenosine
  • Dinoprostone