Melatonin prevents the suppression of cardiac Ca(2+)-stimulated ATPase activity induced by alloxan.
The effects of melatonin treatment on cardiac sarcolemmal membrane function were investigated in alloxan-injected rats. Ca(2+)-stimulated adenosine-triphosphatase (ATPase, Ca2+ pump) and Mg(2+)-ATPase activities were depressed significantly in sarcolemmal preparations from alloxan-injected rats compared with levels in control rats. These deficits were observed 2 days after alloxan injection, and they were accompanied by an increase in the density of voltage-sensitive calcium channels, as measured by the [3H]nitrendipine-binding assay. In a dose-dependent manner, treatment of rats with melatonin before alloxan injection significantly overcame the suppression of Ca(2+)-stimulated ATPase in cardiac sarcolemma. Melatonin (1, 5, and 10 mg/kg) overcame Ca(2+)-stimulated ATPase suppression by 13, 35, and 70%, respectively. In addition, melatonin at a dose of 10 mg/kg also prevented the suppression of the Mg(2+)-ATPase by 31%. The number of [3H]nitrendipine-binding sites was not influenced by melatonin. The patent Na(+)-K(+)-ATPase and ouabain-sensitive Na(+)-K(+)-ATPase activities were not different between the control and experimental groups. The results indicate that Ca2+ pump activity is suppressed by acute alloxan treatment, whereas the density of voltage-sensitive calcium channels is increased. These changes may be a consequence of alloxan toxicity to the cardiac sarcolemma. Melatonin, likely because of its antioxidant capacity, exerts a protective effect on heart sarcolemmal membrane function in alloxan-injected rats.
Chen
L D
LD
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284-7762.
Kumar
P
P
Reiter
R J
RJ
Tan
D X
DX
Manchester
L C
LC
Chambers
J P
JP
Poeggeler
B
B
Saarela
S
S
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D010042:Ouabain; D000496:Alloxan; D009568:Nitrendipine; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D008550:Melatonin; D002118:Calcium