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.