MELATONIN PREVENTS THE SUPPRESSION OF CARDIAC CA2-STIMULATED ATPASE ACTIVITY-INDUCED BY ALLOXAN()

The effects of melatonin treatment on cardiac sarcolemmal membrane fun ction were investigated in alloxan-injected rats. Ca2+-stimulated aden osinetriphosphatase (ATPase, Ca2+ pump) and Mg2+-ATPase activities wer e depressed significantly in sarcolemmal preparations from alloxan-inj ected rats compared with levels in control rats. These deficits were o bserved 2 days after alloxan injection, and they were accompanied by a n increase in the density of voltage-sensitive calcium channels, as me asured by the [H-3]nitrendipine-binding assay. In a dose-dependent man ner, treatment of rats with melatonin before alloxan injection signifi cantly overcame the suppression of Ca2+-stimulated ATPase in cardiac s arcolemma. Melatonin (1, 5, and 10 mg/kg) overcame Ca2+-stimulated ATP ase suppression by 13, 35, and 70%, respectively. In addition, melaton in at a dose of 10 mg/kg also prevented the suppression of the Mg2+-AT Pase by 31%. The number of [H-3]nitrendipine-binding sites was not inf luenced by melatonin. The patent Na+-K+-ATPase and ouabain-sensitive N a+-K+-ATPase activities were not different between the control and exp erimental groups. The results indicate that Ca2+ pump activity is supp ressed by acute alloxan treatment, whereas the density of voltage-sens itive calcium channels is increased. These changes may be a consequenc e of alloxan toxicity to the cardiac sarcolemma. Melatonin, likely bec ause of its antioxidant capacity, exerts a protective effect on heart sarcolemmal membrane function in alloxan-injected rats.