Effect of diadenosine polyphosphates on Ca2+ ATPase activity.
Diadenosine tri-, tetra-, penta-, and hexaphosphate (Ap3A, Ap4A, Ap5A and Ap6A) have been described as having various effects on vascular tone depending on the number of phosphate groups. This study examined the effect of diadenosine polyphosphates on Ca2+ ATPase activity. The activity of the enzyme was measured spectrophotometrically as the difference in hydrolysis of ATP in the presence and absence of Ca2+ with various concentrations of ATP and diadenosine polyphosphates. The diadenosine polyphosphates increased the activity of the Ca2+ ATPase. The effect tended to be stronger with Ap5A and Ap6A than with Ap3A and Ap4A in the order of potency: Ap3A approximately AP4A < Ap5A approximately AP6A. The stimulatory effect of diadenosine polyphosphates was not competitive with that of ATP, suggesting an allosteric activation of Ca2+ ATPase by diadenosine polyphosphates. This effect may be physiologically relevant for limiting the increase in cytosolic free Ca2+ concentration elicited by diadenosine polyphosphates by receptor activation and modulating Ca2+ ATPase function under resting conditions.
Jankowski
J
J
Universitäts-Klinik Marienhospital, Ruhr-Universität Bochum, Herne, Germany.
Schlüter
H
H
Tepel
M
M
Spieker
C
C
Zidek
W
W
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D013329:Structure-Activity Relationship
D015226:Dinucleoside Phosphates; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases