CONTRACTILE HYPERREACTIVITY AND ALTERATION OF PKC ACTIVITY IN GASTRICFUNDUS SMOOTH-MUSCLE OF DIABETIC RATS

Contraction dose dependently induced in gastric smooth muscle of diabe tic rats by Bay K 8644 in the presence of 20 mM KCl was about two time s that induced in controls, and was inhibited more than 50% by 1-(5-is oquinolinesulfonyl)-2-methylpiperazine (H-7). Contraction was caused i n diabetics but usually not in controls by 10(-5) M phorbol 12-myrista te 13-acetate (PMA). In diabetics, this contraction was about 2.5 time s that in controls. Protein kinase C (PKC) activity in the soluble fra ction was depressed by H-7 or staurosporine, and depended on PMA conce ntration, but was greater in diabetics than in controls at any PMA con centration. PKC activity in the soluble fraction was inhibited by lowe r Ca2+ concentration, and was greater in diabetics than in controls. A ffinity and density of binding sites of a Ca2+ channel antagonist liga nd, [H-3]PN200-110, were the same in plasma membrane-enriched fraction s isolated from either controls or diabetic preparations. Thus, hyperr eactivity in diabetic fundus may depend, in part, on alteration of PKC properties, but not on the density of Ca2+ channels.