Extracellular ATP increases intracellular calcium in rat terminal collecting duct via a nucleotide receptor.
Recent studies in a variety of cell types have revealed several receptor subtypes that bind ATP and trigger increases in intracellular Ca2+ concentration ([Ca2+]i). The present studies were aimed at determining whether similar receptors are present in the rat terminal inner medullary collecting duct (IMCD). [Ca2+]i was measured using fura 2 in tubules dissected from collagenase-treated rat kidneys. ATP (1-100 microM) caused a rapid increase in [Ca2+]i with a prolonged late phase after an initial peak. A similar rise was observed in tubules exposed to UTP or to the poorly hydrolyzable analogue, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S). In contrast, agonists that bind P2x, P2y, P2z, and P2t purinergic receptors did not affect [Ca2+]i. Removal of extracellular Ca2+ inhibited the response to ATP by approximately 50% with obliteration of the late phase. Furthermore, indomethacin attenuated the rise in [Ca2+]i produced by ATP. Adenosine analogues also increased [Ca2]i apparently by binding to distinct adenosine receptors rather than to the ATP receptor. We conclude that there is a nucleotide receptor in the rat terminal IMCD, which, when occupied, mobilizes intracellular Ca2+.
Ecelbarger
C A
CA
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Maeda
Y
Y
Gibson
C C
CC
Knepper
M A
MA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017364:Collagenases; D015232:Dinoprostone / Q000096:biosynthesis; D005110:Extracellular Space / Q000378:metabolism*; D016257:Fura-2; D007213:Indomethacin / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology
D011983:Receptors, Purinergic; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; C022571:adenosine 5'-O-(3-thiotriphosphate); D019830:Adenosine-5'-(N-ethylcarboxamide); D000255:Adenosine Triphosphate; D017364:Collagenases; D000241:Adenosine; D015232:Dinoprostone; D002118:Calcium; D016257:Fura-2; D014544:Uridine Triphosphate; D007213:Indomethacin