Extracellular sodium is required for methacholine-induced secretion of mucus glycoconjugates from canine tracheal explants.
Extracellular sodium is known to influence secretion by certain secretory cells, possibly by mobilizing calcium from cellular stores or by altering intracellular pH via regulation of a Na(+)-H+ antiport system. Using canine tracheal explants, we determined whether agents which alter sodium fluxes are capable of modulating basal or cholinergically-induced secretion of mucus glycoconjugates. Methacholine, a cholinergic agonist, increased mucus secretion from explants incubated in the presence or absence of calcium, but had no effect on secretion when incubated in sodium-deficient media, indicating (a) that cholinergically-induced secretion can be mediated by mobilization of cellular calcium and (b) that extracellular sodium was required for this stimulatory effect. Several agents which increase intracellular sodium were tested for their effect on mucus secretion. Ouabain, a sodium pump inhibitor, and veratridine, a sodium channel activator, did not significantly affect control or methacholine-induced secretion; gramicidin, a sodium ionophore, also had no effect on basal release. Tetrodotoxin, a sodium channel inhibitor, was also without effect on basal or methacholine-stimulated mucus release. Agents which alter intracellular pH were also examined for their effects on basal or methacholine-induced glycoconjugate secretion. Amiloride, which decreases intracellular pH by inhibiting Na(+)-H+ exchange, produced a 19 per cent increase in basal secretion (not statistically significant), but had no effect on methacholine-induced secretion. An agent, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which decreases intracellular pH by inhibiting HCO3(-)-Cl- exchange, elicited decreases in both basal and methacholine-induced secretion, but the inhibition did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Hahnemann University, Philadelphia, Pennsylvania 19102.
C
C
Barsigian
E J
EJ
Barbieri
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D046508:Culture Techniques; D004285:Dogs; D006001:Glycoconjugates / Q000378:metabolism*; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D009093:Mucus / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D006001:Glycoconjugates; D008688:Methacholine Compounds; D016210:Methacholine Chloride; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D010042:Ouabain; D014701:Veratridine; D000584:Amiloride; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid