Renal tubular vasopressin receptors downregulated by dehydration.
Receptors for arginine vasopressin (AVP) were characterized in tubular epithelial basolateral membranes (BL membranes) prepared from the kidneys of male Sprague-Dawley rats. Association of [3H]AVP was rapid, reversible, and specific. Saturation studies revealed a single class of saturable binding sites with a maximal binding (Bmax) of 184 +/- 15 fmol/mg protein and a KD of 0.61 +/- 0.04 nM. IC50S for AVP, lysine vasopressin, and oxytocin were 0.74 nM, 9.7 nM, and greater than 1 microM, respectively. The V2 receptor antagonist was more than 3,700 times as effective in displacing [3H]AVP than was the V1 antagonist. To investigate the physiological regulation of vasopressin receptors, the effects of elevated levels of circulating AVP on receptor characteristics were studied. Seventy-two-hour water deprivation significantly elevated plasma osmolality and caused an 11.5-fold increase in plasma [AVP]. Scatchard analysis revealed a 38% decrease in the number of AVP receptors on the BL membranes from dehydrated animals. The high-affinity binding sites on the BL membranes fit the pharmacological profile for adenylate cyclase-linked vasopressin receptors (V2), which mediate the antidiuretic action of the hormone. We conclude that physiologically elevated levels of AVP can downregulate vasopressin receptors in the kidney.
Steiner
M
M
Department of Physiology, University of Florida, Gainesville 32610.
Phillips
M I
MI
D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism; D001667:Binding, Competitive; D003681:Dehydration / Q000097:blood / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000201:enzymology; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology*; D017483:Receptors, Vasopressin; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000254:Sodium-Potassium-Exchanging ATPase