Vasopressin regulation of inner medullary collecting ducts and compensatory changes in mice lacking adenosine A1 receptors.
Activation of adenosine A(1) receptors (A(1)R) can inhibit arginine vasopressin (AVP)-induced cAMP formation in isolated cortical and medullary collecting ducts. To assess the in vivo consequences of the absence of A(1)R, we performed experiments in mice lacking A(1)R (A(1)R(-/-)). We assessed the effects of the vasopressin V(2) receptor (V(2)R) agonist 1-desamino-8-d-arginine vasopressin (dDAVP) on cAMP formation in isolated inner medullary collecting ducts (IMCD) and on water excretion in conscious water-loaded mice. dDAVP-induced cAMP formation in isolated IMCD was significantly greater ( approximately 2-fold) in A(1)R(-/-) compared with wild-type mice (WT) and, in contrast to WT, was not inhibited by the A(1)R agonist N6-cyclohexyladenosine. A(1)R(-/-) and WT had similar basal urinary excretion of vasopressin, expression of aquaporin-2 protein in renal cortex and medulla, and acute increases in urinary flow rate and electrolyte-free water clearance in response to the V(2)R antagonist SR121463 or acute water loading; the latter increased inner medullary A(1)R expression in WT. Dose dependence of dDAVP-induced antidiuresis after acute water loading was not different between the genotypes. However, A(1)R(-/-) had greater inner medullary expression of cyclooxygenase-1 under basal conditions and of the P2Y(2) and EP(3) receptor in response to water loading compared with WT mice. Thus vasopressin-induced cAMP formation is enhanced in isolated IMCD of mice lacking A(1)R, but the adenosine-A(1)R/V(2)R interaction demonstrated in vitro is likely compensated in vivo by multiple mechanisms, a number of which can be "uncovered" by water loading.
Rieg
Timo
T
Department of Medicine , Division of Nephrology and Hypertension, University of California San Diego, San Diego, CA 92161, USA.
Pothula
Kanishka
K
Schroth
Jana
J
Satriano
Joseph
J
Osswald
Hartmut
H
Schnermann
Jürgen
J
Insel
Paul A
PA
Bundey
Richard A
RA
Vallon
Volker
V
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D016133:Polymerase Chain Reaction; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D017483:Receptors, Vasopressin / Q000819:agonists; D014867:Water / Q000378:metabolism*
D019332:Endothelin-1; D008565:Membrane Proteins; C546386:P2ry2 protein, mouse; C545648:Ptger3 protein, mouse; D043682:Receptor, Adenosine A1; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D017483:Receptors, Vasopressin; D014867:Water; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D052250:Nitric Oxide Synthase Type III; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D003894:Deamino Arginine Vasopressin