Platelet Vasopressin Receptors in Patients With Congenital Nephrogenic Diabetes Insipidus
| Title: | Platelet Vasopressin Receptors in Patients With Congenital Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Bichet, Daniel G.; Arthus, Marie-Francoise; Lonergan, Michele |
| Publisher: | Kidney International |
| Date Published: | April 01, 1991 |
| Reference Number: | 325 |
Arginine-vasopressin (AVP), interacts with at least two types of receptors: V1 receptors which mediate the aggregating effects of AVP on human blood platelets and other AVP actions on vascular smooth muscle and hepatocytes; and V2 receptors which mediate the antidiuretic effects on renal tubules. Congenital nephrogenic diabetes insipidus (CNDI) is a rare X-linked disorder in humans with abnormal renal and extrarenal V2-receptor responses. However, the V1 receptor responses are apparently normal, since in these patients blood pressure increases in response to AVP. To assess V1 receptor responses, binding studies (3H-AVP) were done on intact platelets obtained from 6 male patients with CNDI, 10 normal subjects and 4 patients with autosomal dominant central diabetes insipidus (ADCDI). The affinity constant (0.68 +/- 0.04 vs. 0.59 +/- 0.06 nM) and the number of specific binding sites per platelet (101 +/- 6 vs. 86 +/- 12) were similar in the normal subjects and the patients with CNDI. However, the number of binding sites per platelet was increased in the patients with ADCDI (189 +/- 12). Platelet aggregation induced by AVP was equivalent in the three groups. Platelet-fraction AVP was elevated in patients with CNDI and undetectable in patients with ADCDI. These results suggest that the structure and the function of V1 platelet receptor-effector pathway are normal in patients with CNDI.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
In a disorder called X-linked nephrogenic diabetes insipidus (XNDI), the V2Rs both inside and outside the kidney are faulty and either do not bind effectively or at all with AVP. Neither will the V2Rs bind with a synthetically modified form of AVP called DDAVP. This leaves the NDI patient unable to reabsorb water flowing through the collecting duct and unable to concentrate urine. NDI patients are chronically thirsty and have to urinate frequently. There is another form of diabetes insipidus called autosomal dominant central diabetes insipidus (ADCDI) that has symptoms closely matching the symptoms of XNDI. ADCDI is caused by a lack of AVP in the body. XNDI patients have AVP, but they cannot utilize it. ADCDI patients have no AVP to utilize.
There is indirect evidence that the V1Rs of XNDI patients function normally because XNDI patients increase their arterial blood pressure, experience skin blanching and abdominal cramps, and (males) show an increase in production of prostaglandin E2. Bichet, et al., attempted to provide direct proof that XNDI patients had normally functioning V1Rs.
The authors knew that V1Rs were located in platelet membranes and that AVP binding with the V1Rs there caused the platelets to cluster together. (This is called platelet aggregation.) Their previous studies informed the authors that platelet-fraction AVP (a measure of the immune reaction of AVP in platelet-rich plasma) could be used to estimate the incidence of AVP binding to platelet V1Rs. With this in mind, they designed an experiment that would answer three questions:
- Is platelet AVP receptor function normal in XNDI patients?
- Are the number of platelet AVP receptors and the patterns of platelet-aggregation induced by AVP both regulated by the concentration of AVP in the plasma?
- Could platelet-AVP measurements be used to differentiate autosomal dominant central diabetes insipidus (ADCDI) from XNDI?
The researchers conducted tests on 6 XNDI patients, 10 normal patients, and 4 patients with ADCDI. Test results showed that the number of platelet vasopressin receptors, the way these platelets gathered in response to AVP (platelet aggregative characteristics) and platelet-fraction AVP concentrations were similar in normal subjects and in patients with XNDI. Platelet aggregation induced by increasing concentrations of AVP were equivalent in the three groups of subjects. However, ADCDI patients had almost double the specific binding percentages and number of AVP receptors per platelet as did the first two groups. These results provide direct proof that CNDI patients have normal V1Rs located on their platelet membranes.
In addition to the above differences between XNDI and ADCDI patients, platelet-fraction AVP concentrations in ADCDI patients were undetectable, but they were high in XNDI patients. Thus, platelet-fraction measurements may prove valuable in distinguishing patients with XNDI and ADCDI.
At the time of this paper the gene responsible for X-linked NDI was not identified. In addition, it is now clear that patients with autosomal dominant central diabetes insipidus have mutations in the prepro-AVP-NPII gene (Bichet DG. 2000 Polyuria and diabetes insipidus. In: Seldin DW, Giebisch G, eds. The Kidney: Physiology and Pathophysiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1261-1285).