Effect of the choline acetyltransferase inhibitor (2-benzoylethyl)-trimethylammonium iodide (BETA) on human placental prostaglandin release and phospholipase A2 activity.
We investigated the effect of an inhibitor of acetylcholine (ACh) synthesis, (2-benzoylethyl)trimethylammonium iodide (BETA), on prostaglandin (PG)E2 and PGF2 alpha release from incubated placental explants in the presence or absence of ACh or arachidonic acid (AA). BETA alone (100 microM) significantly reduced both PGE2 and PGF2 alpha release. However, this inhibitory effect of BETA was not reversed in the presence of ACh (10 microM to 1 mM). The addition of AA (10 to 100 microM) increased both PGE2 and PGF2 alpha release, and simultaneously overcame the inhibition of PGE2 but not PGF2 alpha release by BETA. These results are compatible with the hypothesis that BETA may be inhibiting the phospholipase A2 (PLA2) step rather than prostaglandin H synthase (PGHS) step in the enzymatic pathway of PG generation. This hypothesis was supported by evidence showing a lack of effect of BETA (10 and 100 microM) on ovine placental microsome PGHS activity. Moreover, human placental homogenate PLA2 activity was reversibly inhibited by BETA (100 microM). In the presence of BETA (100 microM), addition of exogenous ACh (100 microM) had no significant effect on placental PLA2 activity. These results indicate that the inhibitory effect of BETA on placental PG release was unlikely to be via an action on ACh synthesis, but rather via a reversible effect on PLA2 activity.
Chen
Y S
YS
Monash Perinatal Unit, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
King
R G
RG
Rook
T J
TJ
Brennecke
S P
SP
D000109:Acetylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors; D015237:Dinoprost / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012756:Sheep
C017058:(2-benzoylethyl)trimethylammonium; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D002795:Choline O-Acetyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D000109:Acetylcholine