The action of prostaglandins E1 and F2 alpha on adenylate cyclase and cAMP phosphodiesterase was assayed in cell membrane fractions of amnion obtained before and after labor from term physiological pregnancies. Both prostaglandins stimulate the activity of adenylate cyclase in a dose-dependent manner. After spontaneous delivery both prostaglandins stimulate the activity of phosphodiesterase at lower doses and inhibit it at higher ones while the stimulatory effect of low doses is missing before labor. Such a behavior could represent a mechanism for the preservation of the cAMP-mediated processes throughout the entire event of delivery.

The effect of RMI 12330A, an inhibitor of basal as well as serotonin-stimulated adenylate cyclase in the segmental ganglia of the leech Hirudo medicinalis, has been tested on cyclic AMP-phosphodiesterase activity in the same tissue. The drug dose-dependently inhibits high and low affinity enzyme, an effect first evident at an RMI 12330A concentration of 0.5 mM. For both enzyme activities the drug reduces Vmax without substantially influencing Km values. Both basal and serotonin-stimulated adenylate cyclase as well as cyclic AMP-phosphodiesterase activities are inhibited by RMI 12330A in a non-competitive manner.

Basal activity and response to insulin of adenylate cyclase and cyclic AMP-phosphodiesterase were measured in the fetal membranes before and after labor. Basal activity of adenylate cyclase showed only slight variations after delivery when compared to that observed before labor. Enzyme activity was significantly although weakly decreased by insulin both in the amnion and in chorion before labor, while after delivery a weaker non-significant inhibition was observed. Basal activity of cyclic AMP-phosphodiesterase was lower after delivery with respect to that observed before labor. Insulin inhibited enzyme activity in all conditions. Cyclic AMP levels in intact tissue were not substantially modified by insulin.

1. The effects of serotonin, D-ala2met-enkephalinamide, GTP and several non-physiological modulators of adenylate cyclase were examined on cAMP system of the segmental ganglia of the leech Hirudo medicinalis.

The effects of different neuroactive agents on cyclic AMP level of selected ganglia of Planorbis corneus were studied. Serotonin, dopamine and prostaglandin E(2) were capable of increasing significantly cyclic AMP synthesis in all the preparations. When such substances were tested in pairs, supra-additive effects were always observed. In high Ca(2+)-high Mg(2+) solutions dopamine action was blocked, meanwhile serotonin and prostaglandin E(2) were still effective in stimulating cyclic AMP synthesis. In the same experimental condition the supra-additive increases of the nucleotide level by drug combinations disappeared. Serotonin, but not dopamine, significantly stimulated adenylate cyclase activity in all the preparations, while prostaglandin E(2) was effective only in the Viscero-Parietal Complex. The presence of the adenylate cyclase activity in the nervous tissue of Planaorbis was substained by histochemical studies. These results demonstrating that in the nervous system of Planorbis cyclic AMP level is affected by neurotransmitters and neuromodulators, might support the idea of the crucial role of the cyclic nuclotide in the modulation of synaptic transmission.

Adenylate cyclase activity has been measured in segmental ganglia of the leech Hirudo m. Basal enzymatic activity was stimulated in a dose dependent fashion by serotonin. GTP is required in order to evoke maximal stimulation. The effect was blocked by methysergide, an antagonist of serotonin at receptor level. The stimulation of the enzyme was prevented by alpha beta-methy-len-ATP. In addition RMI 12330A inhibited basal as well as serotonin-stimulated adenylate cyclase activity presumably by acting at the catalytic subunit level.