Fixation traps formyl peptide receptors in high and low affinity forms that can be regulated by GTP[S] in the absence of ligand

J Recept Signal Transduct Res. 1996 Jan-Mar;16(1-2):59-75. doi: 10.3109/10799899609039941.

Abstract

The formyl peptide receptor on human neutrophils recognizes bacterial, N-formylated peptides and initiates a cascade of intracellular signals via a pertussis toxin sensitive Gi protein. We used fluorescence techniques to investigate the interactions of ligand (L), receptor (R), and G proteins (G), the ternary complex, in both live and fixed human neutrophils. By lightly fixing permeabilized neutrophils with a procedure that retained ligand binding, we were able to "capture' R and G in different configurations in the absence of ligand. Fixed receptors were trapped in a high affinity form (attributed to LRG) that could not be rapidly converted to low affinity by the addition of GTP[S]. Adding saturating nucleotide prior to fixation trapped receptors in a low affinity form (attributed to LR). The low affinity receptors retained the sensitivity of the native receptors to the presence of NA+. The distribution between high and low affinity receptors was modulated by GTP[S] in a dose dependent manner. The ability to redistribute low and high affinity receptor forms prior to fixation was unique to GTP[S], as compared to other non-activating nucleotides, suggesting that GTP[S] can regulate the distribution between R and RG. We suggest that precoupled receptors that give rise to high affinity ligand binding are likely to exist in native membranes in human neutrophils.

Publication types

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

MeSH terms

  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology*
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Guanylyl Imidodiphosphate / metabolism
  • Humans
  • Kinetics
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism*
  • Neutrophils / cytology
  • Neutrophils / metabolism*
  • Receptors, Formyl Peptide
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / metabolism*
  • Receptors, Peptide / chemistry
  • Receptors, Peptide / drug effects
  • Receptors, Peptide / metabolism*
  • Sodium / metabolism
  • Spectrometry, Fluorescence
  • Substrate Specificity
  • Thionucleotides / metabolism

Substances

  • Receptors, Formyl Peptide
  • Receptors, Immunologic
  • Receptors, Peptide
  • Thionucleotides
  • Guanosine Diphosphate
  • Guanylyl Imidodiphosphate
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • N-Formylmethionine Leucyl-Phenylalanine
  • guanosine 5'-O-(2-thiodiphosphate)
  • Guanosine Triphosphate
  • Sodium