Investigations into the mechanism by which sodium fluoride stimulates prostaglandin production in guinea-pig uterus.
Sodium fluoride (10 mM) caused a slow increase in the outputs of PGF-2 alpha, 6-keto-PGF-1 alpha and, to a lesser extent, PGE-2 from the Day-7 and Day-15 guinea-pig uterus superfused in vitro. This stimulatory action of sodium fluoride was not prevented by using calcium-free Krebs' solution. There was also a faster stimulation of 6-keto-PGF-1 alpha output from the Day-7 guinea-pig uterus produced by sodium fluoride, and this quicker response was abolished by using calcium-free Krebs' solution. TMB-8 (an intracellular calcium antagonist) inhibited the stimulatory action of sodium fluoride on the outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 guinea-pig uterus. W-7 and trifluoperazine (calmodulin antagonists) and neomycin (an inhibitor of phospholipase C) had no inhibitory effect on the increases in outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 guinea-pig uterus produced by sodium fluoride. These results indicate that sodium fluoride slowly stimulates uterine PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha synthesis in the guinea-pig uterus by mobilizing intracellular calcium by a mechanism which apparently does not involve the activation of phospholipase C or the participation of calmodulin (or a related compound). The initial, faster stimulation of 6-keto-PGF-1 alpha synthesis in the Day-7 guinea-pig uterus by sodium fluoride is dependent upon extracellular calcium.
Department of Pharmacology, University of Edinburgh Medical School, UK.
C M
CM
Leckie
N L
NL
Poyser
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D009355:Neomycin / Q000494:pharmacology; D009924:Organ Culture Techniques; D011453:Prostaglandins / Q000096:biosynthesis*; D012969:Sodium Fluoride / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014268:Trifluoperazine / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D011453:Prostaglandins; D014268:Trifluoperazine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D015121:6-Ketoprostaglandin F1 alpha; D005707:Gallic Acid; D012969:Sodium Fluoride; D015237:Dinoprost; D009355:Neomycin; D015232:Dinoprostone