The effect of dimethyl PGE 2 on canine pancreatic autograft exocrine secretion

Abstract

This study was designed to evaluate the effect of 16, 16-dimethyl prostaglandin E 2 (dimethyl PGE 2) on exocrine secretion in autografted animals with pancreaticocystostomies. The rates of secretion of urinary (autograft) amylase (units/min) and bicarbonate (mmole/min), over a 5-hr interval, were determined in the basal state (Group A, N = 5), after a bolus injection of 1 μg/kg of dimethyl PGE 2 (Group B, N = 5), during an OP-CCK infusion at 125 ng/kg/hr (Group C, N = 5), and during an OP-CCK infusion plus a bolus injection of 1 μg/kg (Group D, N = 5) or 18 μg/kg (Group E, N = 5) of dimethyl PGE 2 at the end of the second hour. Basal secretion of amylase and bicarbonate were decreased 1 hr after 1 μg/kg of dimethyl PGE 2, with the bicarbonate inhibition being statistically significant (Group A = 0.073 ± 0.04 vs Group B = 0.001 ± 0.00; P < 0.05). When compared to Group C (128.3 ± 28.0), an immediate and significant inhibition of OP-CCK-stimulated amylase release was demonstrated in both Group D (36.3 ± 11.1; P < 0.02) and Group E (57.3 ± 13.4; P < 0.05). One and two hours post-dimethyl PGE 2, amylase releases were 37.7 ± 8.6 and 64.7 ± 6.8 in Group D and 0.92 ± 0.3 and 8.28 ± 2.6 in Group E, compared to 140.3 ± 23.3 and 104.9 ± 31.8 in Group C, indicating a dose-related, prolonged inhibition of autograft amylase secretion. Bicarbonate secretions immediately and at 1 and 2 hr post-dimethyl PGE 2 were 0.04 ± 0.01, 0.00 ± 0.00, and 0.03 ± 0.01 in Group D and 0.04 ± 0.01, 0.00 ± 0.00, and 0.01 ± 0.00 in Group E, compared to 0.05 ± 0.01, 0.07 ± 0.03, and 0.05 ± 0.02 in Group C. Significant inhibition was present, in both Groups D and E at 1 hr postinfusion only, indicating more transient inhibition of autograft bicarbonate secretion. These studies demonstrate that dimethyl PGE 2 has an inhibitory effect on basal and OP-CCK-stimulated exocrine secretion in a denervated, autograft model. Although the mechanism of inhibition remains to be elucidated, the therapeutic potential of dimethyl PGE 2 in reducing post-transplant exocrine complications warrants further evaluation.