Effect of fenspiride, a non-steroidal antiinflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro.
Neural mechanisms contribute to control of mucus secretion in the airways. Fenspiride is a non-steroidal antiinflammatory agent which has a variety of actions, including inhibition of neurogenic bronchoconstriction. The effect of fenspiride on neurally-mediated mucus secretion was investigated in vitro in electrically-stimulated ferret trachea, using(35)SO(4)as a mucus marker. Cholinergic secretory responses were isolated using adrenoceptor and tachykinin receptor antagonists. Tachykinin responses were isolated using cholinoceptor and adrenoceptor antagonists. Electrical stimulation increased cholinergic secretion by;90% and tachykininergic secretion by;40%. Fenspiride (1 microM-1 mM) tended to inhibit cholinergic secretion in a concentration-dependent manner, although only at 1 mM was inhibition (by 87%) significant. Inhibition by fenspiride of tachykininergic secretion was not concentration-dependent, and again significant inhibition (by 85%) was only at 1 mM. Inhibition was not due to loss of tissue viability, as assessed by restitution of secretory response after washout. Fenspiride also inhibited secretion induced by acetylcholine, but did not inhibit substance P-induced secretion. Histamine receptor antagonists increased basal secretion by 164%, whereas fenspiride did not affect basal secretion. We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism.
Khawaja
A M
AM
Thoracic Medicine, National Heart & Lung Institute (Imperial College), Dovehouse Street, London, UK.
Liu
Y C
YC
Rogers
D F
DF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004558:Electric Stimulation; D005289:Ferrets / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D009093:Mucus / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D013141:Spiro Compounds / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006633:Histamine Antagonists; D018040:Receptors, Neurokinin-1; D013141:Spiro Compounds; D013431:Sulfates; D013462:Sulfur Radioisotopes; D013373:Substance P; D015288:Neurokinin A; C084775:fenspiride