Saturday, 08.08.2020

Barry Blackwell: The lithium controversy. A historical autopsy (Collated)

Janos Radó: Addition to final comment
Calcitonin in lithium-induced nephrogenic diabetes insipidus

 

In our previous studies the favorable antidiuretic action of Desmopresssin was counteracted by the concomittant administration of Calcitonine in Lithium-induced permanent nephrogenic diabetes insipidus  (Radó 2018). However, the exact mechanism of the abolishment of Desmopressin-induced  antidiuresis by Calcitoninewas not clear. As the opinions in the literature are rather divided concerning the basic water metabolic action of Calcitonine, further considerations may have significance.

            Calcitonine is a tricky” hormone, having both diuretic and antidiuretic properties. Diuretic effect of Calcitonine was an observation mainly in the older literature (Carney, and Thompson 1981;Keeler, Walker and Copp 1970) and is in harmony with our published data on a water mobilizing action (Radó 1991,1993,2018). On the other hand, a water retaining action was found by the de Rouffignac group (Elalouf, Roinel and de Rouffignac 1986in response to human Calcitonine in rats during micropunture studies simulating the changes induced by Desmopressin. The results of these investigations were later confirmed by elegant sophisticated methods (Bouley 2011) indicating that Calcitonine has a vasopressin-like action, indeed. Calcitonine was even recommended-though purely on theoratical basis- for the treatment of nephrogenic diabetes insipidus, i.e., in a vasopressin resistant condition (Bouley et al. 2011).

An alternative explanation tothe complicated water effects of Calcitonine may be provided by supposing that both Desmopressin and Calcitonine have aneffect onthe same renal tubular site onthe vasopressin (V2) receptor, but the effect of Calcitonine is weaker than that of Desmopressin. So, Calcitonine, by occupying the receptors, can have a competitive antagonism with the Desmopressin molecule. Further studies are necessary to confirm or exclude the possible competitive antagonism beetwen Desmopressin and Calcitonine.

 

References:

Bouley R, Lu HA, Nunes P, Da Silva N, McLaughlin M, Chen Y, Brown D.Calcitonin Has a Vasopressin-like Effect on Aquaporin-2 Trafficking and Urinary Concentration. J Am Soc Nephrol 22: 2011. doi: 10.1681/ASN.2009121267.

Carney S, Thompson L. Acute effect of calcitonin on rat renal electrolyte transport. Am J Physiol 240: F12–F16, 1981.

Elalouf JM, Roinel N, de Rouffignac C.Effects of human calcitonin on water and electrolyte movements in rat juxtamedullary nephrons: inhibition of medullary K recycling. Pflugers Arch. 1986 May;406(5):502-8.

Keeler, R. Walker, V. Copp D. H. Natriuretic and diuretic effects of salmon calcitonin in rats. Canadian Journal of Physiology and Pharmacology, 1970, Vol. 48, No. 12 : pp. 838-841.

Radó JP, Zdravkova S. Lithium-induced chronic water-metabolism disorder (nephrogenicdiabetes insipidus). Orv Hetil. 1991;132, 1987-90.

Radó JP, Zdravkova S. Effect of Indomethacine and Calcitonine During Administration of 1-Deamino-8-D-Arginin-Vasopressin (dDAVP) on Free Water Clearance in NephrogenicDiabetes Insipidus (NDI). XIIth International Congress of Nephrology. June 13–18, 1993, Jerusalem, Israel.

Radó J. Use of modern antidiuretic agents in the treatment of permanent lithium induced nephrogenic diabetes insipidus. (Administration of excessive doses of desmopressin resulted in clinically relevant antidiuresis, enhanced by indomethacine and abolished by calcitonine). inhn.org. Controversies. January 25, 2018. (Janos Radó’s final commenton Barry Blackwell: The lithium controversy. A historical autopsy. Collated by Olaf Fjetland).

 

September 13, 2018