Effects of prostaglandin E2 and cyclooxygenase inhibitors on clustering and level of nicotinic acetylcholine receptor in mouse myotubes co-cultured 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 microM) decreased both indices in a concentration-dependent manner. Aspirin and indomethacin, cyclooxygenase inhibitors, increased the indices at 1.0 microM and 10-30 nM, and decreased them at higher concentrations of 10-30 microM and 0.1-1 microM, respectively. Prostaglandin F2 alpha (PGF2 alpha, 1-10 microM), nordihydroguaiaretic acid (30 microM), a lipoxygenase inhibitor, and PAF (10 microM) 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.