ABSTRACT
OBJECTIVE: This study was undertaken to investigate the regulation of prostaglandin release by oxytocin and the influence of oxytocin on intracellular calcium and on the cyclic adenosine monophosphate system in human amnion-derived WISH cells. STUDY DESIGN: We determined prostaglandin E(2) release from WISH cells treated with oxytocin, evaluated the cytosolic calcium concentration in single WISH cells by confocal microscopy, and measured both intracellular cyclic adenosine monophosphate levels and adenylyl cyclase activity after oxytocin treatment. RESULTS: Treatment of WISH cells with oxytocin resulted in a concentration-dependent release of prostaglandin E(2), which was increased by lithium chloride and inhibited by indomethacin and U-73122. In single WISH cells, oxytocin increased cytosolic calcium. Moreover, the hormone lowered levels of intracellular cyclic adenosine monophosphate but did not alter adenylyl cyclase activity. CONCLUSIONS: Our data demonstrate, for the first time, that WISH cells respond to oxytocin by increasing prostaglandin E(2) release. In addition to phospholipase C activation and cytosolic calcium increase, the hormone effect involves also a reduction of the cyclic adenosine monophosphate level.
Subject(s)
Amnion/drug effects , Amnion/metabolism , Calcium/metabolism , Cyclic AMP/metabolism , Dinoprostone/metabolism , Oxytocin/pharmacology , Adenylyl Cyclases/metabolism , Cell Line , Enzyme Inhibitors/pharmacology , Estrenes/pharmacology , Female , Humans , Indomethacin/pharmacology , Lithium Chloride/pharmacology , Pregnancy , Pyrrolidinones/pharmacology , Tocolytic Agents/pharmacology , Type C Phospholipases/antagonists & inhibitorsABSTRACT
The ability of adenosine agonists to modulate the electrically evoked release of acetylcholine (ACh) from [3H]choline preloaded guinea-pig superior cervical ganglia (SCG) was investigated. The adenosine A1-receptor selective agonist N6-cyclohexyladenosine (CHA) and 2-chloroadenosine (2-CADO) inhibited the evoked transmitter release, the effect being reversed by the A1-receptor selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and by sulmazole (SUL), which blocks both the A1-receptor and the adenylate cyclase inhibitory regulator Gi. In whole ganglia, CHA decreased both the basal and the forskolin (FSK)-stimulated cyclic AMP synthesis. The latter effect was again prevented by the A1 antagonist DPCPX. These results are compatible with the existence, in the guinea-pig SCG, of adenosine A1-receptors, part of which are located on the presynaptic nerve terminals mediating an inhibition of ACh release.
