title: Selective modulation by guanine nucleotides of the high affinity subset of plasma membrane receptors for leukotriene B4 on human polymorphonuclear leukocytes.
abstract: Isolated human polymorphonuclear (PMN) leukocyte plasma membranes express high affinity (mean Kd = 0.12 nM) and low affinity (mean Kd = 50 nM) receptors for the chemotactic factor leukotriene B4 (5(S),12(R)-dihydroxy-eicosa-6,14 cis-8,10 trans-tetraenoic acid; LTB4) that are similar to those on intact PMN leukocytes. A portion of high affinity LTB4-R on PMN leukocyte membranes were converted to the low affinity state by GTP (mean +/- SE = 28.6 +/- 14.0%) and nonhydrolyzable GTP analogues, such as 5'-guanylylimidodiphosphate (GMP-PNP), in a concentration-dependent, nucleotide-specific, and reversible manner, without altering the intrinsic binding affinities of either class. [3H]GMP-PNP bound specifically to one class of receptors (mean Kd = 13 nM) on PMN leukocyte membranes. The interdependence of the LTB4-binding membrane protein and guanine nucleotide-binding protein was suggested by the capacity of LTB4 to enhance by a maximum of 150% the binding of [3H]GMP-PNP to PMN leukocyte membranes by increasing the number, but not altering the affinity, of receptors for GMP-PNP. Pertussis toxin, but not cholera toxin, reversed the enhancement of binding of [3H]GMP-PNP produced by LTB4. Guanine nucleotide-binding proteins and high affinity LTB4-R thus exhibit a mutual regulation that differs mechanistically from that of peptide chemotactic factor receptors on PMN leukocytes.
authors.affiliation: Department of Medicine, University of California Medical Center, San Francisco 94143.
authors.forename: J W
authors.initials: JW
authors.lastname: Sherman
authors.forename: E J
authors.initials: EJ
authors.lastname: Goetzl
authors.forename: C H
authors.initials: CH
authors.lastname: Koo
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011971:Receptors, Immunologic / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D018102:Receptors, Leukotriene B4; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D010566:Virulence Factors, Bordetella; D007975:Leukotriene B4; C004805:5'-guanylylmethylenebisphosphonate; D006157:Guanosine Monophosphate; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D037342:Pertussis Toxin; D006152:Cyclic GMP