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Mucosa‐dependent muscarinic liberation of prostaglandins from rat isolated trachea
Author(s) -
Brunn Gemot,
Wessler Ignaz,
Racke Kurt
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16403.x
Subject(s) - muscarinic acetylcholine receptor , acetylcholine , carbachol , endocrinology , chemistry , medicine , arachidonic acid , prostaglandin , muscarinic acetylcholine receptor m3 , pirenzepine , muscarinic agonist , methoctramine , prostaglandin e2 , receptor , stimulation , biology , biochemistry , enzyme
1 The present study examined whether cholinoceptor stimulation modulates the release of arachidonic acid‐derived mediators from rat isolated tracheae. 2 Tracheae were preincubated with [ 3 H]‐arachidonic acid and the outflow of 3 H‐compounds was determined. Acetylcholine and the muscarinic agonist, carbachol but not nicotine, increased the rate of tritium outflow maximally by about 30%. The M 3 receptor‐preferring antagonist p ‐fluoro‐hexahydrosiladiphenidol was more effective than pirenzepine and methoctramine in antagonizing the effect of acetylcholine. 3 High performance liquid chromatography analysis (methanol gradient) of the released 3 H‐compounds showed that one peak, co‐eluting with [ 14 C]‐prostaglandin E 2 ([ 14 C]‐PGE 2 ) and [ 3 H]‐PGD 2 , was enhanced almost 10 fold following muscarinic receptor activation, whereas the outflow of [ 3 H]‐arachidonic acid remained unaffected. 4 Using an acetonitril gradient separation it was shown that [ 3 H]‐PGE 2 , [ 3 H]‐PGD 2 and [ 3 H]‐PGF 2α are released spontaneously, but [ 3 H]‐PGE 2 represented the major fraction of 3 H‐prostaglandins. Acetylcholine enhanced the release of all three 3 H‐prostaglandins, but the effect on PGE 2 was most pronounced and most consistent. 5 After removal of the mucosa the muscarinic effect of acetylcholine on total tritium and on that of the 3 H‐prostaglandins ([ 3 H]‐PGE 2 /PGD 2 peak) was abolished. 6 Acetylcholine also enhanced the outflow of radioimmunologically determined PGE 2 in a mucosa‐dependent manner. 7 After inhibition of cyclo‐oxygenase by 3 μM indomethacin, the outflow of 3 H‐prostaglandins was reduced to almost undetectable levels and acetylcholine evoked a marked release of [ 3 H]‐arachidonic acid. The phospholipase A 2 inhibitor, quinacrine (up to 100 μm) also blocked the effect of acetylcholine on the outflow of 3 H‐prostaglandins, but this was not followed by a compensatory increase in the outflow of [ 3 H]‐arachidonic acid. 8 In conclusion, activation of muscarinic receptors which have characteristics of the M 3 subtype can evoke release of prostaglandins from the airway mucosa.