Beta-adrenoceptor-mediated facilitation of endogenous noradrenaline release from rat isolated trachea.
Overflow of endogenous noradrenaline from rat isolated trachea was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine and tyrosine. Isoprenaline 100 nmol/l increased the evoked overflow of noradrenaline by about 65%. This effect was antagonized by propranolol (100 nmol/l) and the beta 2-selective adrenoceptor antagonist ICI 118,551 (100 nmol/l), but not by the beta 1-selective adrenoceptor antagonist CGP 20712 A (100 nmol/l). The beta 2-selective adrenoceptor agonist formoterol (1-100 nmol/l) also facilitated the evoked overflow of noradrenaline, but maximally by only about 25% at 10 nmol/l, i.e. formoterol behaved as a partial agonist at these facilitatory beta-adrenoceptor. This assumption is also supported by the observation that formoterol (10 nmol/l) acted as antagonist against isoprenaline (100 nmol/l). Mechanical removal of the mucosa resulted in a 30% decrease in tissue noradrenaline and a 55% reduction of the evoked overflow of noradrenaline. In mucosa-denuded preparations isoprenaline failed to facilitate noradrenaline overflow. In the presence of indomethacin (3 mumol/l) the evoked overflow of noradrenaline from mucosa containing preparations was increased by about 50%, but isoprenaline still further facilitated the evoked noradrenaline overflow by about 40%. In conclusion, the overflow of noradrenaline in the rat trachea is facilitated via beta 2-adrenoceptors, an effect which requires an intact airway mucosa.
Brunn
G
G
Department of Pharmacology, University of Frankfurt, Germany.
Wessler
I
I
Anderson
G P
GP
Maclagan
J
J
Racké
K
K
D018663:Adrenergic Agents / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D014132:Trachea / Q000294:innervation / Q000378:metabolism*
D018663:Adrenergic Agents; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine; D007213:Indomethacin