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 mu M) 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'-0-(3-thiotriphosphate) (ATP gamma S). In contrast, agonists that bind P-2x, P-2y, P-2z, and P-2t purinergic receptors did not affect [Ca2+](i). Removal of extracellular Ca2+ inhibited the response to ATP by similar to 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+.