A possible explanation for the refractoriness of uterine prostaglandin production.
Arachidonic acid increased the outputs of prostaglandin (PG) F-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus superfused in vitro. Similar increases in PG output were observed when the arachidonic acid treatment was repeated after an interval of 1, 3 or 5 h. Phospholipase (PL) A-2 increased the outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 guinea-pig uterus, but repeating the PLA-2 treatment 1 h later failed to stimulate PG output. The increase in outputs of PGF-2 alpha and PGE-2 caused by PLA-2 were partly restored after 3 h and were fully restored after 5 h, whereas the increase in 6-keto-PGF-1 alpha output produced by PLA-2 was only partly restored after 3 and 5 h. PLA-2 had little or no effect on PGF-2 alpha and PGE-2 outputs from the Day-15 guinea-pig uterus initially, and when repeated after 1, 3 and 5 h. This was probably due to the output of these two PGs, particularly of PGF-2 alpha, being stimulated in vivo before removal of the uterus. PLA-2 increased 6-keto-PGF-1 alpha output from the Day-15 uterus initially, but failed to cause a response when administered again 1 h later. After 3 and 5 h, the increase in 6-keto-PGF-1 alpha output from the Day-15 uterus caused by PLA-2 was partly restored. A23187 and PLC increased the outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus. These responses to A23187 and PLC were reduced (but not abolished) when the two compounds were administered again 1 h later. After 3 and 5 h, the increases in output of PGF-2 alpha and PGE-2 produced by A23187 and PLC had returned to the initial values. The increases in output of 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus produced by A23187 and PLC were partly restored after 3 and 5 h, except for the response to PLC on Day 7 which was fully restored after 5 h. The results show that there is no failure with time in the mechanism which converts arachidonic acid into PGF-2 alpha in the guinea-pig uterus.(ABSTRACT TRUNCATED AT 400 WORDS)
Poyser
N L
NL
Department of Pharmacology, University of Edinburgh Medical School, UK.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006168:Guinea Pigs; D009924:Organ Culture Techniques; D010477:Perfusion; D010741:Phospholipases A / Q000494:pharmacology; D013268:Stimulation, Chemical; D013997:Time Factors; D010738:Type C Phospholipases / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D010741:Phospholipases A; D010738:Type C Phospholipases; D015232:Dinoprostone