Lithium induced polyuria and renal vasopressin receptor density.
BACKGROUND
Lithium, a drug frequently used for treatment of affective disorders, is known to cause a vasopressin-resistant state, leading to polyuria and polydipsia. It has been suggested that lithium interacts with the renal V2-vasopressin receptor. Detailed studies on the influence of lithium on the AVP receptor, however, have so far been difficult due to the lack of a suitable radioligand with high specific activity and high affinity.


METHODS
Using 125I-[8-(p-(OH)-phenylpropionyl)]- LVP, we studied the effects of lithium on V2-vasopressin receptors in male Sprague-Dawley rats and LLC-PK1 cells. Rats, having free access to water, were orally treated with 10 mg lithium/100 mg b.w./day or placebo for 10 days. Scatchard analysis was performed using membranes prepared from homogenized renal papillae.


RESULTS
Lithium caused significant polyuria and an impaired renal concentration capacity after water deprivation. Binding studies showed no effect of lithium on binding affinity KD (0.98 +/- 0.21 nmol/l vs. 0.86 +/- 0.15 nmol/l (Li) (n.s.). Receptor density, however, significantly decreased from 130 +/- 12.3 nmol/kg protein in controls (n = 8) to 101.7 +/- 13.4 nmol/kg protein (n = 8), (P < 0.05). Plasma osmotically and AVP were not significantly altered by lithium treatment. Vasopressin receptor density on LLC-PK1-cells, a pig renal cell line, was not changed by preincubation with lithium (312 +/- 22 nmol/kg vs. 329 +/- 25 nmol/kg (Li) (n = 6, n.s.).


CONCLUSIONS
The decrease of AVP-receptor density in vivo might be related to vasopressin resistance, either primary, or secondary to other factors, e.g. actual water transport.
Hensen
J
J
Department of Medicine, Universitäts-Klinikum Steglitz, Freie Universtiät Berlin, Germany.
Haenelt
M
M
Gross
P
P
D000818:Animals; D001127:Arginine Vasopressin / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism; D018374:LLC-PK1 Cells / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000633:toxicity*; D008297:Male; D011141:Polyuria / Q000139:chemically induced* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D014868:Water Deprivation
D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D008094:Lithium