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.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Nakagawa
M
M
Kobayashi
S
S
Kimura
M
M
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002450:Cell Communication; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D010972:Platelet Activating Factor / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D010972:Platelet Activating Factor; D011978:Receptors, Nicotinic; D009637:Masoprocol; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin