The pharmacologic modulation of mediator release from human basophils.
We have characterized the effects of eight different drugs on the IgE-mediated histamine release (HR) and leukotriene C4 (LTC4R) from human basophils. Arachidonic acid analogues 5,8,11 eicosatriynoic acid and 5,8,11,15 eicosatetraynoic acid inhibit the release of both mediators in the range 10(-6) to 10(-4) mol/L with almost total (80% to 100%) inhibition of release at 10(4) mol/L. The inhibition of LTC4R was significantly (p less than 0.05) greater than the inhibition of HR only at intermediate (10(-5) to 3 X 10(-5) mol/L) doses of the drugs. Two other inhibitors of phospholipase A2 (bromophenacyl bromide and phenidone) affected the release of both mediators equally. Two drugs that activate adenylate cyclase (prostaglandin E1 and dimaprit) inhibited release in a dose-dependent fashion but failed to preferentially affect either HR or LTC4R. Isoproterenol (10(-6) to 10(-4) mol/L), a third activator of adenylate cyclase, caused only moderate (30%) inhibition of HR, even when the reaction was staged, but was slightly (0.1 less than p less than 0.05) more potent against leukotriene release. The final drug tested was the phosphodiesterase inhibitor, isobutylmethylxanthine, which proved to be an effective (50% to 100%) inhibitor of both mediators in the range 10(-5) to 10(-3) mol/L.
Warner
J A
JA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md 21239.
MacGlashan
D W
DW
Peters
S P
SP
Kagey-Sobotka
A
A
Lichtenstein
L M
LM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D017259:Dimaprit; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D013189:SRS-A / Q000378:metabolism*; D013890:Thiourea / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D013189:SRS-A; D015117:5,8,11,14-Eicosatetraynoic Acid; C026603:5,8,11-eicosatriynoic acid; D000242:Cyclic AMP; D000527:Alprostadil; D013890:Thiourea; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine; D017259:Dimaprit