Protective effect of heparin on immunologically induced tracheal smooth muscle contraction in vitro.
Our previous studies have shown that heparin, a competitive inhibitor of inositol triphosphate receptors, inhibits airway anaphylaxis in vivo. In the present study, we tested the hypothesis that heparin blocks immunologically induced tracheal smooth muscle (TSM) contraction in vitro. TSM was obtained from sheep allergic to Ascaris suum antigen, and was suspended in an organ bath containing oxygenated (95% O2, 5% CO2) Krebs-Henseleit buffer at 39 degrees C. After an equilibration period, the tissues were treated with heparin dissolved in 10 microliters DMSO, at concentrations of 1, 10, or 100 U/ml (final concentration in the bath). Two types of controls were used: vehicle (10 microliters DMSO)-treated tissues and tissues treated with the anti-asthmatic nedocromil sodium (10(-5) M). After 30 min pretreatment, tissues were challenged with 10, 30 and 100 microliters of antigen. Contractions induced by antigen were expressed as percentage of the contraction elicited by the maximum effective concentration of acetylcholine (ACh, 10(-2) M). Antigen produced dose-dependent increases in tension, which were blocked by heparin and nedocromil sodium; maximal inhibition was 43 and 52%, respectively. Neither heparin nor nedocromil sodium affected the dose-response curve or the maximum response to Ach. The addition of the heparin preservative (benzyl alcohol) did not reverse ACh-induced contractions, or inhibit antigen-induced contractile responses. These results suggest that heparin blocks immunologically induced TSM contraction, without affecting the contractile response to the airway smooth muscle agonist, ACh. This action of heparin is similar to that of the anti-asthmatic nedocromil sodium and may be related to inhibition of mast cell mediator release.
Abraham
W M
WM
Division of Pulmonary Disease, University of Miami School of Medicine, Miami Beach, Fla., USA.
Abraham
M K
MK
Ahmed
T
T
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000947:Antigens, Helminth / Q000494:pharmacology; D017165:Ascaris suum / Q000276:immunology; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects* / Q000276:immunology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000276:immunology*; D017835:Nedocromil / Q000494:pharmacology; D012756:Sheep; D014132:Trachea
D018926:Anti-Allergic Agents; D000947:Antigens, Helminth; D001592:Benzyl Alcohols; D017835:Nedocromil; D006493:Heparin; D019905:Benzyl Alcohol; D004121:Dimethyl Sulfoxide