Induction of Glomerulopressin Production by Cyclic AMP

Summary

Isolated rat livers were perfused with gassed Krebs-Ringer-Bicarbonate and different doses of theophylline and dibutyryl cyclic AMP were added to the perfusing solution. The perfusates were ultrafiltrated through Diaflo UM-05 membranes. The glomerulopressin activity of the ultrafiltrates were assayed in the tonic tension contraction (TTC) of isolated stomach fundus from rats. As glomerulopressin is known to be a glucuronide, it was inactivated with β-glucuronidase to confirm that the effect on the stomach fundus was due to the glomerulopressin and not to another substance.

It was observed that doses of theophylline between 2 × 10^-3M and 2 × 10^-5M enhanced glomerulopressin production. However, there was no relationship between dose of theophylline and the response, and a dose of theophylline 2 × 10^-6M has no activity. The perfusion with dibutyryl cyclic AMP at 5 × 10^-8M increased the amount of glomerulopressin produced by the liver. This was a log-dose response of glomerulopressin production to dibutyryl cyclic AMP between 5 × 10^-8 M and 5 × 10^-4M.

Theophylline (2 × 10^-6M) potentiated the activity of cyclic AMP (5 × 10^-8 M).

These results support the view that cyclic AMP is the intracellular mediator of the hepatic production of glomerulopressin.

Key-Words:

Liver - Theophylline - Glucuronides