Physiologic regulation and distribution of the renal vasopressin receptor.
Previous studies suggest that circulating levels of vasopressin (AVP) influence the responsiveness of the kidney to AVP. To determine how changes in renal AVP receptors and adenylate cyclase (AC) contribute to such altered responsiveness, we analyzed AVP receptors and AVP-sensitive AC in kidneys from Sprague-Dawley, Long-Evans and homozygous Brattleboro rats. In autoradiographic studies, the distribution of [3H]AVP binding sites was similar in all groups, corresponding to the location of AVP-sensitive AC: collecting ducts greater than outer medullary collecting ducts greater than medullary thick ascending limb greater than cortical collecting ducts. No differences in AVP receptor affinity or content were observed in kidney medullary membranes from Sprague-Dawley, Long-Evans or Brattleboro rats (KD = 0.8, 0.9, and 0.7 nM; Bmax = 116 +/- 9, 95 +/- 11 and 98 +/- 6 fmol/mg). Basal and AVP-stimulated AC activities were lower in kidney membranes from Brattleboro rats compared with Sprague-Dawley and Long-Evans animals (basal = 28 +/- 4, 40 +/- 4 and 38 +/- 3 pmol cAMP/mg/min; EDmax = 57 +/- 5, 80 +/- 7 and 71 +/- 2 pmol cAMP/mg/min) with no change in ED50. In 48-hour water-deprived Sprague-Dawley rats, AVP receptors were decreased from 116 +/- 9 to 58 +/- 2 fmol/mg, suggesting that AVP receptors are down-regulated by elevated AVP blood levels. The absence of changes in basal or AVP-stimulated AC in dehydrated rats indicates that receptor-AC coupling is normal and that maximum AC activation can occur with partial receptor occupancy. The data also indicate that impaired renal responsiveness to AVP in Brattleboro rats is not due to down-regulation of AVP receptors.
Finkel
M S
MS
Hypertension-Endocrine Branch, NHLBI, Bethesda, Md.
Mendelsohn
F A
FA
Quirion
R
R
Zamir
N
N
Keiser
H R
HR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D007668:Kidney / Q000648:ultrastructure*; D008566:Membranes; D011863:Radioimmunoassay; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000502:physiology*; D017483:Receptors, Vasopressin; D014667:Vasopressins / Q000097:blood
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D000262:Adenylyl Cyclases