EFFECTS OF PROSTAGLANDIN-E2 AND CYCLOOXYGENASE INHIBITORS ON CLUSTERING AND LEVEL OF NICOTINIC ACETYLCHOLINE-RECEPTOR IN MOUSE MYOTUBES COCULTURED WITH SPINAL-CORD EXPLANT

The clustering and level of nicotinic acetylcholine receptor (n-AChR) in cultured mouse myotubes are negatively controlled by endogenous phospholipase A2 (PLA2) (Kimura et al., Int. J. Devl. Neurosci. 5, 127-133, 1987). The effects of PLA2-related metabolites, prostaglandins, leukotrienes and platelet-activating factor (PAF) were investigated using fluorescein isothiocyanate-alpha-bungarotoxin. Peak and total fluorescence within a cluster were used as indices of clustering and level of n-AChR, respectively. Prostaglandin E2 (PGE2, 1-10-mu-M) decreased both indices in a concentration-dependent manner. Aspirin and indomethacin, cyclooxygenase inhibitors, increased the indices at 1.0-mu-M and 10-30 nM, and decreased them at higher concentrations of 10-30-mu-M and 0.1-1-mu-M, respectively. Prostaglandin F2-alpha (PGF2-alpha, 1-10-mu-M), nordihydroguaiaretic acid (30-mu-M), a lipoxygenase inhibitor, and PAF (10-mu-M) had no effect. These results suggest that the control of endogenous PLA2 on the clustering and level of n-AChR is due to PGE2, but not to PGF2-alpha, leukotrienes or PAF.