Nephrol Dial Transplant (1996) 11: 622-627
© 1996 European Renal Association-European Dialysis and Transplant Association
research-article
Lithium induced polyuria and renal vasopressin receptor density
Department of Medicine, Divisions of Endocrinology and Nephrology, Universitäts-Klinikum Steglitz, Freie Universität Berlin Friedrich-Alexander-Universität Erlangen-Nuremberg Med. Klinik I, Germany
Correspondence and offprint requests to: Correspondence and offprint requests to: Johannes Hensen, M.D., Department of Medicine I, Division of Endocrinology and Metabolism, Krankenhausstr, 12, 91054 Erlangen, Germany
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 osmolality 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.
Keywords: lithium; vasopressin; polyuria; vasopressin receptor; vasopressin resistance
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