Effect of melittin on prostaglandin production by guinea-pig uterus.
Melittin, an activator of phospholipase (PL) A-2, increased the outputs of prostaglandin (PG) F-2 alpha and 6-keto-PGF-1 alpha, but not of PGE-2, from Day-7 guinea-pig uterus superfused in vitro. Reducing the extracellular calcium concentration (by omitting calcium chloride from the superfusing fluid) partially inhibited the stimulatory effect of melittin on uterine PG production. TMB-8 (an intracellular calcium antagonist) completely prevented the stimulation of PGF-2 alpha and 6-keto-PGF-1 alpha output by melittin, although the production of both PGs tended to increase after stopping the melittin and TMB-8 treatments. TMB-8 also inhibited the increases in outputs of PGF-2 alpha, 6-keto-PGF-1 alpha and PGE-2 and prevented contraction of the uterus induced by exogenous PLA-2. Trifluoperazine (a calmodulin antagonist) had no inhibitory effect on the increases in outputs of PGF-2 alpha and 6-keto-PGF-1 alpha produced by melittin; it potentiated the stimulatory effect of melittin on 6-keto-PGF-1 alpha output and allowed melittin to increase PGE-2 output. When melittin was applied twice to the superfused uterus with an interval of 1 h between each treatment, partial refractoriness of the responses to melittin was seen: the magnitudes of the increases in PGF-2 alpha and 6-keto-PGF-1 alpha outputs were 40-50% less after the second treatment than after the first treatment. These results show that melittin stimulates the synthesis of PGF-2 alpha and PGI-2 (measured as 6-keto-PGF-1 alpha) in guinea-pig uterus by mechanisms which are calcium dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
F A
FA
Department of Pharmacology, University of Edinburgh Medical School, UK.
Poyser
N L
NL
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000378:metabolism; 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; D008555:Melitten / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011453:Prostaglandins / Q000096:biosynthesis*; D014268:Trifluoperazine / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D011453:Prostaglandins; D008555:Melitten; D014268:Trifluoperazine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D015121:6-Ketoprostaglandin F1 alpha; D005707:Gallic Acid; D015237:Dinoprost; D015232:Dinoprostone; D002118:Calcium