Arachidonic acid increases cholinergic secretory responsiveness of ferret tracheal glands

Abstract

The purpose of this study was to determine if arachidonic acid could alter ferret tracheal gland secretory responsiveness to a cholinergic agonist. We prepared glandular explants and incubated the explants in medium containing [3H]glucosamine. Secretory responsiveness was expressed as the percent change in basal secretion of acid-precipitable [3H]glucosamine-labeled glycoconjugates induced by the addition of agonist with and without arachidonic acid [mean +/- SE (n)]. Addition of 10(-3) M arachidonic acid caused a significant increase in secretion [28 +/- 6% (n = 6)] compared with untreated control tissues [-10 +/- 4% (n = 7), P less than or equal to 0.05]. Carbachol (10(-7) M) increased secretion 39 +/- 9% (n = 7). The combination of 10(-3) M arachidonic acid and 10(-7) M carbachol elicited a significantly greater change in secretion compared with either agent alone [173 +/- 50% (n = 5)]. The addition of nordihydroguaiaretic acid (10(-6) M) or indomethacin (10(-6) M) partially attenuated the arachidonic acid-enhanced secretory responsiveness to carbachol. Treatment with both blockers completely inhibited the arachidonic acid-enhanced secretory responsiveness to carbachol. The effect of arachidonic acid on cholinergic stimulation was also abolished by treating the explant cultures with tetrodotoxin (10(-7) M). This hypersecretory state is most likely mediated by eicosanoid-induced release of neurotransmitters from nerve terminals.