Selective modulation by guanine nucleotides of the high affinity subset of plasma membrane receptors for leukotriene B4 on human polymorphonuclear leukocytes.
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.
Sherman
J W
JW
Department of Medicine, University of California Medical Center, San Francisco 94143.
Goetzl
E J
EJ
Koo
C H
CH
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
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