MUSCARINIC CILIOSTIMULATION REQUIRES ENDOGENOUS PROSTAGLANDIN PRODUCTION

Prostaglandin E2 (PGE2) is a known modulator in upper airway ciliary a ctivity and may be involved in the transduction of the muscarinic acet ylcholine receptor signal. We studied the in vitro effects of muscarin ic 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 ade noid explants significantly increased ciliary beat frequency. This eff ect was blocked by the application of diclofenac, a cyclooxygenase inh ibitor. Using radioimmunoassay, PGE2 production was measured during ci liostimulation with methacholine. Methacholine produced a significant increase in production in PGE2 during ciliostimulation. The roles of p hospholipase C and phospholipase A2 in prostaglandin production were i nvestigated by inhibiting these enzymes. D609, a phospholipase C inhib itor, significantly inhibited ciliary beat frequency increase and PGE2 production during methacholine stimulation. However, PACOCF3, a phosp holipase A2 inhibitor did not block ciliary bent frequency increase or PGE2 production in response to methacholine. These data show that pho spholipase C is required for PGE2 production and ciliostimulation.