DURATION-DEPENDENT CHANGES IN CALCIUM RESPONSIVENESS IN THE ALLOXAN-DIABETIC RAT INTESTINE

Disturbances of the gastrointestinal tract that are common in diabetes mellitus seem to be related to intestinal motility. In experimental m odels of diabetes, decreased calcium sensitivity has been demonstrated in various smooth muscles including those in the gastrointestinal tra ct. The main purpose of the present study was to examine further the c alcium sensitivity in diabetic rat intestine and to understand if chan ges in the calcium sensitivity occur at an earlier stage of the diseas e, For this purpose, the effects of potassium and calcium were evaluat ed on nondepolarized and depolarized duodenum from rats with alloxan d iabetes for 1 and 8 weeks and their age-matched controls. To evaluate the calcium sensitivity in rat duodenum, apparent affinity constants ( pD(2) values) and intrinsic activities (alpha(E) values) were calculat ed for every experimental conditions examined in this study, Both valu es (pD(2) and alpha(E)) for the effects of potassium and calcium on th e nondepolarized and depolarized duodenum, respectively, were not, cha nged in 1-week diabetic rats. In contrast, intrinsic activities for th e effects of potassium and calcium were found to be significantly decr eased (p < 0.001) in the nondepolarized and depolarized duodenum from rats with alloxan diabetes for 8 weeks, whereas apparent affinity cons tants were not altered in this case. Taking into consideration all the se experimental findings, the decreased calcium sensitivity in gastroi ntestinal tract seems to be closely related to decreased calmodulin le vels and may occur at a later stage of diabetes as a linkage to long-t erm gastrointestinal complications.