The Effects of Synthetic Human and Salmon Calcitonins on Electrolyte Excretion in the Rat

Abstract

S U M M A R Y1. The effects on renal electrolyte excretion of human and salmon synthetic calcitonins were studied in the rat.2. As little as 50 ng of salmon calcitonin produced an increase in sodium excretion, but human calcitonin in doses up to 15 pg had only a slight effect.3. Small doses of both hormones decreased urinary calcium and magnesium. Larger doses of salmon calcitonin produced less depression of calcium and magnesium excretion even in the presence of a greater fall in plasma calcium.4. The mechanisms responsible for these effects and the possible therapeutic implications are discussed.

Kidney and Calcitonin

“…A rdaillou et al [4] found a marked increase in the urinary excretion of sodium and chloride during intravenous infusion of CT in man. A similar effect was reported in man [14], rat [55,66], cow [11], sheep [12] and rabbit [58], Salmon CT has a more potent natriuretic effect than porcine and human CT in both man [30] and the rat [66], This effect on sodium excretion reflects probably an inhibition of sodium reabsorption in the proxi mal tubule. P aillard et al [51] found that the ratio of free water clearance to creatinine clearance was markedly increased following salmon CT injection in normal subjects in whom ADH secretion was inhibited, providing indirect evidence for inhibition of proximal sodium reabsorption by the hormone.…”

“…The latter mechanism has been postulated by M unson [48] but not yet demon strated. In favor of such an hypothesis is the study of W est et al [66] showing that previous hypocalcaemia potentiates the effect of a calcium load on CT secretion. G ittes et al [27] also demonstrated a high calcitonin content in thyroids from hypocalcaemic rats.…”

“…This effect of CT did not de pend on any modification of PTH or aldosterone secretion. It was observed in PTX rats [66], patients with hypoparathyroidism [6,30], and normal subjects in whom PTH secretion was inhibited by a mild increase in plasma calcium [51]. Increased sodium excretion following CT administration was also ob served in patients in whom aldosterone action was inhibited by spirolactone [4], In the same study, covariance analysis showed that sodium excretion was independent of calcium excretion.…”

“…From micropuncture studies in the rat, L eG rimellec and Lechene [38] con cluded that secretion of endogenous CT produced an increase in the proximal tubular reabsorption of magnesium. H aas et al [30] observed an increase in potassium excretion in man which was found neither by A rdaillou et al [6] using porcine CT, nor by Paillard et al [51] using salmon CT. N ielsen et al [50] also reported an increase in potassium excretion in the rat during intra venous infusion of porcine synthetic CT. All these changes in magnesium and potassium excretion have also been observed in PTX rats [66] and in patients with hypoparathyroidism [30,61]. The only study devoted to the renal ex cretion of H + ions after CT administration is that of A rdaillou et al [5] who observed no effect in human subjects.…”

“…The de monstration that synthetized porcine CT [2,33,50], human CT [29,37,67] and salmon CT [37,51,66] produced similar effects to purified porcine hormone excluded the possibility that the phosphaturia was due to impurities of the preparation. Increase in phosphaturia was observed in a variety of species after CT administration including rat [1,2,44,60,66], sheep [12], pig [57], cow [11] and rabbit [58], Only in the dog was CT without effect [17,52], Studies in man were numerous [18,19,29,37,40,47,51 ] and gave similar results. A direct phosphaturic effect of CT in man could be separated from that due to the in crease in endogenous PTH since similar results were observed in normal sub jects and in patients with hypoarathyroidism [30,51,61].…”