Dynorphin binds to neuropeptide Y and peptide YY receptors in human neuroblastoma cell lines

Am J Physiol. 1994 Nov;267(5 Pt 1):E702-9. doi: 10.1152/ajpendo.1994.267.5.E702.

Abstract

The modulation of neuropeptide Y (NPY) and peptide YY (PYY) receptors by dynorphin, luteinizing hormone-releasing hormone (LHRH), corticotropin-releasing factor (CRF), and cholecystokinin octapeptide has been studied in human neuroblastoma cell lines SK-N-MC and SMS-MSN, which express Y1 and Y2 receptors for NPY/PYY. Dynorphin A and LHRH inhibited the binding of NPY/PYY to SK-N-MC cell membranes at concentrations ranging from 10(-7) to 10(-5) M, whereas dynorphin A and CRF were effective in SMS-MSN cells. The inhibitory effect of dynorphin A on NPY/PYY binding was observed in the presence of guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analogue, as well as H-7 and H-8, novel inhibitors of protein kinases C and A. However, U-50488, the most potent kappa-selective compound did not mimic the dynorphin action. Dynorphin A showed neither effect on the dissociation of NPY/PYY from their receptors nor inhibition on the basal as well as forskolin-stimulated adenosine 3',5'-cyclic monophosphate response. These results indicate that the interaction of dynorphin A with Y1 and Y2 receptors is not mediated by changes in receptor-G protein interaction, receptor phosphorylation, and allosteric binding to NPY/PYY receptors but that dynorphin A binds to NPY/PYY receptors at high concentrations, probably in an antagonistic manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Corticotropin-Releasing Hormone / pharmacology
  • Dynorphins / metabolism*
  • Dynorphins / pharmacology
  • Gonadotropin-Releasing Hormone / pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Humans
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Protein Kinase Inhibitors
  • Receptors, Gastrointestinal Hormone / drug effects
  • Receptors, Gastrointestinal Hormone / metabolism*
  • Receptors, Neuropeptide Y / drug effects
  • Receptors, Neuropeptide Y / metabolism*
  • Sincalide / pharmacology
  • Tumor Cells, Cultured

Substances

  • Protein Kinase Inhibitors
  • Receptors, Gastrointestinal Hormone
  • Receptors, Neuropeptide Y
  • peptide YY receptor
  • Gonadotropin-Releasing Hormone
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Dynorphins
  • Corticotropin-Releasing Hormone
  • Sincalide