Purinergic regulation of basal and arginine vasopressin-stimulated hydraulic conductivity in rabbit cortical collecting tubule.
An extracellular adenosine responsive site that stimulates adenylate cyclase activity has been identified in several tissues. There is limited information on the presence and physiologic significance of adenosine receptors in well-defined segments of the mammalian nephron. We therefore examined the effect of adenosine and selected analogues on basal hydraulic conductivity in rabbit cortical collecting tubules (CCT) perfused in vitro. Adenosine and analogues with an intact ribose moiety produced a significant, sustained increase in hydraulic conductivity. No increase in hydraulic conductivity was seen in either time control CCT's or CCT's exposed to an adenosine analogue with an altered ribose moiety. These experiments are compatible with the presence of a functional adenosine receptor which requires an intact ribose moiety and acts to increase hydraulic conductivity in the mammalian CCT. An intracellular adenosine responsive site, termed the "P site," which inhibits adenylate cyclase activity, has also been described in several tissues. We therefore examined the effect of a P site agonist on hydraulic conductivity responses to arginine vasopressin, forskolin and cAMP. P site stimulation with 2'5' dideoxyadenosine inhibited the effect of AVP and of forskolin but not of cAMP to increase hydraulic conductivity. These results are compatible with a functional P site in the rabbit CCT which acts at the catalytic subunit of adenylate cyclase to inhibit hydraulic conductivity. Together, these results demonstrate purinergic modulation of basal and arginine vasopressin-stimulated water flux in the mammalian collecting tubule.
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism*; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011983:Receptors, Purinergic; D012266:Ribose; D014882:Water-Electrolyte Balance
D003839:Deoxyadenosines; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D001127:Arginine Vasopressin; D005576:Colforsin; D016048:Dideoxyadenosine; D012266:Ribose; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000241:Adenosine