Prostanoids inhibit release of endogenous norepinephrine from rat isolated trachea.
Prostanoids, of epithelial origin, are known as modulators of several processes in the airways. The present study examined whether prostanoids are involved in the local control of sympathetic neurotransmission. The release of endogenous norepinephrine from rat isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine, and tyrosine. In different series of experiments, indomethacin (3 mumol/L) increased the evoked release of endogenous norepinephrine by 70 to 80%. In the presence of indomethacin, prostaglandin E2 (PGE2) and several prostanoid receptor agonists inhibited the evoked release of norepinephrine in a concentration-dependent manner, maximally by 60 to 70%. According to the concentration producing 35% inhibition of norepinephrine release (half-maximal effect), the following rank order of potencies was observed (EC35): nocloprost (8 nmol/L), sulprostone (30 nmol/L), PGE2 (308 nmol/L), iloprost (2 mumol/L), and U46619 (> 10 mumol/L). The EP1 receptor antagonist AH 6809 (3 mumol/L) had no effect on the evoked norepinephrine release and did not affect the inhibitory effect of 1 mumol/L of sulprostone. In the absence of indomethacin, the inhibitory effect of PGE2 was similar to that observed in the presence of indomethacin. After removal of the epithelium, the evoked norepinephrine release was markedly reduced. However, no significant effect of indomethacin was observed in epithelium-denuded tracheae. In conclusion, norepinephrine release in the rat trachea is inhibited via prostaglandin receptors that have the pharmacologic characteristics of the EP3 subtype. Endogenous eicosanoids, most likely of epithelial origin, are involved in the local control of the release of norepinephrine.
Racké
K
K
Departments of Pharmacology, University of Frankfurt, Germany.
Bähring
J
J
Langer
C
C
Bräutigam
M
M
Wessler
I
I
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004848:Epithelium / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011453:Prostaglandins / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects; D014132:Trachea / Q000737:chemistry / Q000187:drug effects* / Q000294:innervation
D011453:Prostaglandins; D011941:Receptors, Adrenergic; D011451:Prostaglandin-Endoperoxide Synthases; D009638:Norepinephrine; D007213:Indomethacin