Relaxation of canine airway smooth muscle by the heparin preservative benzyl alcohol.
To characterize the actions of heparin and its common preservative benzyl alcohol (BA) on airway smooth muscle functions, we studied the effects of purified heparin, commercial heparin salt solution (HSS) containing heparin and BA, and BA on the contractile responses of canine bronchial segments to various agonists under isometric conditions in vitro. Addition of HSS or the equivalent volume of BA reversibly depressed acetylcholine-induced contraction in a dose-dependent fashion, IC50 values being 5.7 +/- 1.1 (SE) mM of BA, whereas purified heparin had no effect. This depression was not affected by pretreatment of tissues with propranolol, indomethacin or ouabain, or removal of epithelium, and BA at sufficient concentrations to cause muscle relaxation did not alter intracellular adenosine 3',5'-cyclic monophosphate contents. BA also attenuated the contractile responses to electrical field stimulation, histamine, and serotonin, but it was without effect on those to KCl. In addition, the acetylcholine-induced enhancement of hydrolysis of phosphatidylinositol 4,5-biphosphate in the lipid fraction and the resultant production of phosphatidic acid were inhibited in the presence of BA. These results suggest that the heparin preservative BA but not heparin relaxes airway smooth muscle, probably through the decrease in intracellular Ca2+ release by inhibiting agonist-mediated phosphatidylinositol turnover.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Kanemura
T
T
Horii
S
S
Chiyotani
A
A
Sakai
N
N
Kobayashi
K
K
Takizawa
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004848:Epithelium / Q000502:physiology; D006493:Heparin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D010592:Pharmaceutic Aids; D010712:Phosphatidic Acids / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D011310:Preservatives, Pharmaceutical; D011433:Propranolol / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014316:Tritium
D001592:Benzyl Alcohols; D001593:Benzyl Compounds; D010592:Pharmaceutic Aids; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D011310:Preservatives, Pharmaceutical; D014316:Tritium; D010042:Ouabain; D006493:Heparin; D011433:Propranolol; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D019905:Benzyl Alcohol; D000109:Acetylcholine; D007213:Indomethacin