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ANTAGONISM BY MANGANESE OF ISOPRENALINE DILATATION OF THE GUINEA‐PIG ISOLATED TRACHEA
Author(s) -
Jamieson Dana D.,
Quinnf R. J.,
Coutier A.
Publication year - 1983
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1983.tb00219.x
Subject(s) - isoprenaline , chemistry , histamine , acetylcholine , dilator , guinea pig , antagonism , bronchodilatation , manganese , endocrinology , medicine , pharmacology , biology , biochemistry , bronchodilator , receptor , organic chemistry , stimulation , asthma
SUMMARY 1. Manganese (0.5‐100 μmol/1) was found to be a potent inhibitor of the dilator effect of isoprenaline on the isolated tracheal muscle of the guinea‐pig. Above these concentrations the inhibitory action of Mn 2+ diminished and no inhibition occurred above 1000 μmol/I Mn 2+ . Thus a bell‐shaped dose‐response curve resulted for the inhibition of isoprenaline by Mn 2+ . The antagonism was surmountable but apparently noncompetitive. 2. Dilation of the isolated trachea caused by theophylline or nitroprusside was not inhibited by Mn 2+ at concentrations of 12.5 to 750 μmol/1. 3. At the dose range which could be tested manganese did not antagonize isoprenaline bronchodilatation in vivo. However, manganese at doses between 0.5 and 2.0 μmol/kg inhibited increases in pulmonary resistance caused by acetylcholine, histamine or serotonin. 4. At concentrations above 250 μmol/1 Mn 2+ inhibited constrictor responses to histamine, acetylcholine and serotonin in guinea‐pig isolated ileum and trachea, and inhibited serotonin and prostaglandin E 2 contractions in rat fundus. 5. Co 2+ , Fe 2+ , Fe 3+ and Zn 2+ were also tested for their action against isoprenaline on the isolated trachea. Co 2+ was similar in effect to Mn 2+ but had only 1/50 of the potency. Up to the highest concentrations which could be tested, namely 1000 μmol/1, the other trace metals produced negligible effects. 6. Thus Mn 2+ showed selective inhibition of the relaxant effect of isoprenaline on the guinea‐pig isolated trachea, at concentrations of Mn 2+ well below those shown previously to inhibit constrictor responses by block of transmembrane Ca 2+ entry. It is suggested that Mn 2+ may interfere with intracellular Ca 2+ fluxes in the isolated trachea.