Pentagastrin-stimulated DNA synthesis in mouse gut is influenced by the circadian system

Gastrin is trophic for rodent gut mucosa. Proglumide, a competitive inhibitor of gastrin, can exert an antitrophic effect and can block pentagastrin-stimulated DNA synthesis. We have examined the influence of the circadian system on pentagastrin-stimulated DNA synthesis in the murine stomach (glandular and nonglandular stomach) and colon. We studied 224 male CD2F₁ mice divided into four groups. Group A was ad lib fed (controls). Groups B, C, and D received 6-9 intraperitoneal injections of either NaCl, pentagastrin or pentagastrin + proglumide, at 8-h intervals prior to sacrifice. Mice from each group (A-D) were killed (by cervical dislocation) at 3-h intervals for 24 h. Incorporation of tritiated thymidine (DNA synthesis) was measured, and significant (p<0.001) circadian rhythms were found, which were not eliminated after treatment with either pentagastrin or pentagastrin + proglumide. DNA synthesis in the glandular stomach increased significantly after treatment with pentagastrin, but only during the span of time when DNA synthesis was increasing also in control mice; it had no effect at other times. Proglumide blocked the effect of pentagastrin only during the time of increasing DNA synthesis; it had no effect at other times. The identical regimen given at different times in the circadian cycle yielded significantly different results. In the intact animal, studies on the effects of various stimulators or inhibitors of DNA synthesis should be time-qualified.