Growth regulation of primary human keratinocytes by prostaglandin E receptor EP2 and EP3 subtypes

Raymond L. Konger, Rama Malaviya, Alice P. Pentland

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

We examined the contribution of specific EP receptors in regulating cell growth. By RT-PCR and northern hybridization, adult human-keratinocytes express mRNA for three PGE2 receptor subtypes associated with cAMP signaling (EP2, EP3, and small amounts of EP4). In actively growing, non-confluent primary keratinocyte cultures, the EP2 and EP4 selective agonists, 11- deoxy PGE1 and I-OH PGE1, caused complete reversal of indomethacin-induced growth inhibition. The EP3/EP2 agonist (misoprostol), and the EP1/EP2 agonist (17-phenyl trinor PGE2), showed less activity. Similar results were obtained with agonist-induced cAMP formation. The ability of exogenous dibutyryl cAMP to completely reverse indomethacin-induced growth inhibition support the conclusion that growth stimulation occurs via an EP2 and/or EP4 receptor-adenylyl cyclase coupled response. In contrast, activation of EP3 receptors by sulprostone, which is virtually devoid of agonist activity at EP2 or EP4 receptors, inhibited bromodeoxyuridine uptake in indomethacin- treated cells up to 30%. Although human EP3 receptor variants have been shown in other cell types to markedly inhibit cAMP formation via a pertussis toxin sensitive mechanism, EP3 receptor activation and presumably growth inhibition was independent of adenylyl cyclase, suggesting activation of other signaling pathways.

Original languageEnglish (US)
Pages (from-to)221-234
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1401
Issue number2
DOIs
StatePublished - Feb 4 1998

    Fingerprint

Keywords

  • (Human)
  • Cyclic AMP
  • Keratinocyte
  • Proliferation
  • Prostaglandin E receptor
  • Receptor agonist

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this