[Mechanisms of tolerance to sulfur dioxide and sodium metabisulfite].
Inhalation of sulphur dioxide (250 ppm), (SO2) or sodium metabisulfite (80 mM) (MBS) aerosol or perfusion with MBS (3 mM) induced a reduction in compliance and conductance in the isolated, perfused and ventilated guinea pig lung. Pretreatment of the lung with sodium sulfite (3 mM), a dissolution product of SO2 and MBS, reduced the bronchoconstriction induced by SO2 and MBS. Bronchoconstriction induced by SO2 and MBS in associated to increased levels of Calcitonin gene-Related Peptide (CGRP) in the perfusate effinent, indicating activation of sensory nerves. The release of CGRP induced by SO2 and MBS was not affected by sodium sulfite. Sulfite treatment did not modify lung reactivity towards acethylcholine, bradykinin, serotonin, histamine and substance P (fragment 5-11). An inhibitory effect by sulfite was observed on bronchoconstriction induced by neurokinin A (fragment 4-10). Since bronchoconstriction induced by SO2 and MBS appears to be mediated by neurokinin A release and action, sulfite may act by affecting its signal transduction pathway. In conclusion, the results indicate that during exposure to some environmental and occupational pollutants, e.g. SO2 and MBS, critical modifications of sulfhydryl groups on smooth muscle receptors may occur. We hypothesise this as a possible step in the development of tolerance and hyperreactivity.
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Dipartimento di Tossicologia, Sez. Patologia Generale, Università degli Studi di Cagliari.
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Cannas
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Congiu
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D000280:Administration, Inhalation; D000336:Aerosols; D000393:Air Pollutants / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004361:Drug Tolerance; D006168:Guinea Pigs; D008170:Lung Compliance / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010477:Perfusion; D015398:Signal Transduction / Q000187:drug effects*; D013447:Sulfites / Q000008:administration & dosage / Q000494:pharmacology*; D013458:Sulfur Dioxide / Q000008:administration & dosage / Q000494:pharmacology*
D000336:Aerosols; D000393:Air Pollutants; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D013447:Sulfites; D013458:Sulfur Dioxide; C005200:sodium metabisulfite; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide