A possible explanation for the refractoriness of uterine prostaglandin production

• Published in: Journal of reproduction & fertility Vol. 91; no. 1; pp. 371 - 384
• Main Author: Poyser, N L
• Format: Journal Article
• Language: English
• Published: England Society for Reproduction and Fertility 01-01-1991
• Subjects: 6-Ketoprostaglandin F1 alpha - biosynthesis; Animals; Arachidonic Acids - pharmacology; Calcimycin - pharmacology; Dinoprost - biosynthesis; Dinoprostone - biosynthesis; Female; Guinea Pigs; Organ Culture Techniques; Perfusion; Phospholipases A - pharmacology; Stimulation, Chemical; Time Factors; Type C Phospholipases - pharmacology; Uterus - drug effects; Uterus - metabolism
• ISSN: 1470-1626; 0022-4251; 1741-7899
• DOI: 10.1530/jrf.0.0910371

Arachidonic acid increased the outputs of prostaglandin (PG) F-2α, PGE-2 and 6-keto-PGF-1α 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-2α, PGE-2 and 6-keto-PGF-1α 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-2α 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-1α output produced
by PLA-2 was only partly restored after 3 and 5 h. PLA-2 had little or no effect on PGF-2α 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-2α, being stimulated in vivo before removal of the uterus. PLA-2 increased 6-keto-PGF-1α 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-1α output from the Day-15 uterus
caused by PLA-2 was partly restored. A23187 and PLC increased the outputs of PGF-2α, PGE-2 and 6-keto-PGF-1α 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-2α and PGE-2 produced by A23187 and PLC had
returned to the initial values. The increases in output of 6-keto-PGF-1α 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-2α in the guinea-pig
uterus. The refractoriness of uterine PGF-2α production following repeated stimulation apparently occurs at the level of arachidonic
acid release, particularly as regards the action of PLA-2. There appear to be one or several pools of bound arachidonic acid
which are readily releasable but which take 3–5 h to refill completely. This phenomenon may explain, in part, the pulsatile
nature of uterine PGF-2α release.
Keywords: guinea-pig; uterus; phospholipase A-2; phospholipase C; A23187; arachidonic acid; prostaglandins