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1. The present study examined whether cholinoceptor stimulation modulates the release of arachidonic acid-derived mediators from rat isolate tracheae. 2. Tracheae were preincubated with [3H]-arachidonic acid and the outflow of 3H-compounds was determined. Acetylcholine and the muscarinic agonist, carbachol but not nicotine, increased the rate of tritium outflow maximally by about 30%. The M3 receptor-preferring antagonist rho-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 3H-compounds showed that one peak, co-eluting with [14C]-prostaglandin E2([14C]-PGE2) and [3H]-PGD2, was enhanced almost 10 fold following muscarinic receptor activation, whereas the outflow of [3H]-arachidonic acid remained unaffected. 4. Using an acetonitril gradient separation it was shown that [3H]-PGE2, [3H]-PGD2 and [3H]-PGF2alpha are released spontaneously, but [3H]-PGE2 represented the major fraction of 3H-prostaglandins. Acetylcholine enhanced the release of all three 3H-prostaglandins, but the effect on PGE2 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 3H-prostaglandins ([3H]-PGE2/PGD2 peak) was abolished. 6. Acetylcholine also enhanced the outflow of radioimmunologically determined PGE2 in a mucosa-dependent manner. 7. After inhibition of cyclo-oxygenase by 3 microM indomethacin, the outflow of 3H-prostaglandins was reduced to almost undetectable levels and acetylcholine evoked a marked release [3H]-arachidonic acid. The phospholipase A2 inhibitor, quinacrine (up to 100 microM) also blocked the effect of acetylcholine on the outflow of 3H-prostaglandins, but this was not followed by a compensatory increase in the outflow of [3H]-arachidonic acid. 8. In conclusion, activation of muscarinic receptors which have characteristics of the M3 subtype can evoke release of prostaglandins from the airway mucosa.
G Brunn, and
I Wessler, and
K Racké
December 1976,
Nihon Heikatsukin Gakkai zasshi,
G Brunn, and
I Wessler, and
K Racké
May 1992,
Biulleten' eksperimental'noi biologii i meditsiny,
G Brunn, and
I Wessler, and
K Racké
February 1989,
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology,
G Brunn, and
I Wessler, and
K Racké
August 1985,
General physiology and biophysics,
G Brunn, and
I Wessler, and
K Racké
March 1980,
British journal of pharmacology,
G Brunn, and
I Wessler, and
K Racké
November 1992,
The American review of respiratory disease,
G Brunn, and
I Wessler, and
K Racké
November 1994,
Naunyn-Schmiedeberg's archives of pharmacology,
G Brunn, and
I Wessler, and
K Racké
March 1978,
Prostaglandins,
G Brunn, and
I Wessler, and
K Racké
August 1997,
The European respiratory journal,
G Brunn, and
I Wessler, and
K Racké
November 1981,
Prostaglandins,
