Muscarinic ciliostimulation requires endogenous prostaglandin production.
Prostaglandin E2 (PGE2) is a known modulator in upper airway ciliary activity and may be involved in the transduction of the muscarinic acetylcholine receptor signal. We studied the in vitro effects of muscarinic ciliostimulation on ciliary beat frequency (CBF) and PGE2 in human adenoid explants to determine whether PGE2 production is an essential step in the signal transduction mechanism. Methacholine applied to adenoid explants significantly increased ciliary beat frequency. This effect was blocked by the application of diclofenac, a cyclooxygenase inhibitor. Using radioimmunoassay, PGE2 production was measured during ciliostimulation with methacholine. Methacholine produced a significant increase in production in PGE2 during ciliostimulation. The roles of phospholipase C and phospholipase A2 in prostaglandin production were investigated by inhibiting these enzymes. D609, a phospholipase C inhibitor, significantly inhibited ciliary beat frequency increase and PGE2 production during methacholine stimulation. However, PACOCF3, a phospholipase A2 inhibitor, did not block ciliary beat frequency increase or PGE2 production in response to methacholine. These data show that phospholipase C is required for PGE2 production and ciliostimulation.
Gayner
S M
SM
Department of Otorhinolaryngology, Mayo Clinic, Rochester, MN 55905, USA.
McCaffrey
T V
TV
D000109:Acetylcholine / Q000378:metabolism; D000234:Adenoids / Q000378:metabolism / Q000473:pathology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D002923:Cilia / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007659:Ketones / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009636:Norbornanes; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D054467:Phospholipases A2; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013726:Terbutaline / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology
D000318:Adrenergic beta-Agonists; D001952:Bridged-Ring Compounds; D018678:Cholinergic Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007659:Ketones; D018721:Muscarinic Agonists; D009636:Norbornanes; D011976:Receptors, Muscarinic; D013859:Thiocarbamates; D013871:Thiones; C109341:palmitoyl trifluoromethyl ketone; D016210:Methacholine Chloride; D004008:Diclofenac; C046498:tricyclodecane-9-yl-xanthogenate; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D015232:Dinoprostone; D013726:Terbutaline; D000109:Acetylcholine