0.48-29.9 mkM/kg (Male NMRI mic)

The rate of acid secretion and mucosal cyclic adenosine 3',5'-monophosphate (cyclic AMP) content have been measured on the same guinea-pig isolated stomach preparation in response to ICI 63197, a potent phosphodiesterase inhibitor. The stomach was divided into two halves along the greater curvature and each half was tied over the end of a short perspex tube, mucosal surface facing the lumen. The muscle coat was not removed. The serosal surface was bathed with a bicarbonate buffered saline and gassed with 95% 2 and 5% CO2 whilst the mucosal surface was bathed with a similar but unbuffered saline gassed with 100% O2. The volume of serosal bathing fluid was 30 ml and the rate of acid secretion was determined by titration with 20 mM NaOH. Following dissection, the preparations were set up in the tissue bath and gassed for 1 h before addition of ICI-63197. The mucosal saline was changed every 15 min and the rate of spontaneous acid secretion determined. After the addition of drug (ICI-63197), acid secretion was measured for four further 15 min periods. The rate associated with the drug was taken as the average of the last two such periods. Tissues were then taken from the bath and placed in ice cold saline before extraction for cyclic AMP assay.