Summary
In order to evaluate whether or not the action of salmon calcitonin (sCT) at the kidney level could be mediated through specific receptors for the hormone, we have studied the effects of sCT infusions on urinary excretion of cyclic nucleotides in humans. Parallel in vitro studies have been conducted by evaluating the effects of sCT on cyclic nucleotide levels in primary cultures of cortical and medullary human kidney cells.
In vivo experiments showed that sCT induced an increase in cGMP in human urine, which was rapid and short-lasting, being superimposable on the increase of urinary excretion of calcium and magnesium. The increase of inorganic phosphate urinary excretion was delayed and appeared to parallel that of urinary cAMP. On the other hand, our in vitro experiments showed that sCT stimulated the guanylate cyclase—cGMP system of human kidney cortical cells at nanomolar concentrations, while higher concentrations of the hormone were required to activate the adenylate cyclase—cAMP system. In addition, sCT was not able to significantly modify the cellular levels of either nucleotide in human kidney medullary cells.
Present data demonstrated a direct effect of sCT on human kidney cortical cGMP production, while the efficacy of sCT on the kidney cortex adenylate cyclase—cAMP system appears to be delayed and/or reduced.
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References
Robinson CJ, Martin TJ, MacIntyre I (1966) Phosphaturic effect of thyrocalcitonin. Lancet 2:83–84
Caniggia A, Gennari C (1976) Fisiopatologia Clinica del metabolismo fosfocalcico, Pozzi L, Roma, p 255
Haas HG, Dambacher MA, Guncaga J, Lauffenburger T (1971) Renal effects of calcitonin and parathyroid extract in man. J Clin Invest 50:2689–2702
Murad F, Pak CYC (1972) Urinary excretion of adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate. N Engl J Med 286:1382–1387
Gennari C, Lorè F, Nuti R (1979) Paratormone, calcitonina ed AMP ciclico. In: De Bastiani G et al. (eds) Calcitonina: nuove acquisizioni e prospettive. Fondazione Carlo Erba, Milano, pp 9–19
Marx SJ, Aurbach GD (1975) Renal receptors for calcitonin: coordinate occurence with calcitonin-activated adenylate cyclase. Endocrinology 97:448–453
Aurbach GD, Heath DA (1974) Parathyroid hormone and calcitonin regulation of renal function. Kidney Int 6:331–345
Vigo PL, Milhaud G, Peracchi M, Girardello R, Ortolani S, Polli EE (1980) Plasma immunoreactive N-terminal parathyroid hormone and cyclic AMP and cyclic GMP urinary levels in man after i.m. administration of two different doses of porcine calcitonin. Biomedicine 33:255–259
Kaminsky NI, Broadus AE, Hardman JG, Jones DJ Jr, Ball JH, Sutherland EW, Liddle GW (1970) Effects of parathyroid hormone on plasma and urinary adenosine 3′,5′-monophosphate in man. J Clin Invest 49:2387–2395
Toccafondi RS, Aterini S, Medici MA, Rotella CM, Tanini A, Zonefrati R (1980) Thyroid stimulating antibody (TSAb) detected in sera of patients using human thyroid cell cultures. Clin Exp Immunol 40:532–539
Zonefrati R, Brandi ML, Rotella CM, Selli C, Toccafondi R (1982) Parathyroid hormone bioassay using human kidney cortical cells in primary culture. Acta Endocrinol (in press)
Brown BL, Albano BM, Ekins RP, Sgerzi AM, Tampion W (1971) A simple and sensitive saturation assay method for the measurement of adenosine 3′,5′-cyclic monophosphate. Biochem J 121:561–562
Steiner AL, Parker CW, Kipnis DM (1972) Radioimmunoassay for cyclic nucleotides. J Biol Chem 247:1106–1113
Kissane JM, Robins E (1958) The fluorometric measurement of deoxyribonucleic acid in animal tissue with special reference to the central nervous system. J Biol Chem 233:184–188
Paillard F, Ardaillou R, Malendin H, Fillastre J-P, Prier S (1972) Renal effects of salmon calcitonin in man. J Lab Clin Med 80:200–216
Hershe JNM, Marcus R, Aurbach JD (1974) Calcitonin and the formation of 3′,5′-AMP in bone and kidney. Endocrinology 94:241–247
Goldberg ND, O'Dea RF, Hoddox MK (1973) Cyclic GMP. In: Greengard P, Robinson GA (eds) Advances in cyclic nucleotides research. Raven Press, New York, p 155
Broadus AE, Kaminsky NI, Hardman JG, Sutherland EW, Liddle GW (1970) Kinetic parameters and renal clearances of plasma adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in man. J Clin Invest 49:2222–2236
Caniggia A, Gennari C, Vattimo A, Nardi P, Nuti R, Galli M (1976) Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man. Calcif Tissue Res 20:209–215
Broadus AE, Kaminsky NI, Northcutt RC, Hardman JG, Sutherland EW, Liddle GW (1970) Effects of glucagon on adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in human plasma and urine. J Clin Invest 49:2237–2245
Ball JK, Kaminsky NI, Hardman JG, Broadus AE, Sutherland DW, Liddle GW (1972) Effects of catecholamine and adrenergic-blocking agents on plasma and urinary cyclic nucleotides in man. J Clin Invest 51:2124–2131
Chabardes D, Gagnan-Brunette M, Imbert-Teboul M, Goutcherevskaia O, Montegut M, Clique A, More F (1980) Adenylate cyclase responsiveness to hormones in various portions of the human nephron. J Clin Invest 65:439–448
Kim JK, Frohmnert PP, Hui YSF, Barnes LD, Farrow GM, Dousa T (1977) Enzymes of cyclic 3′,5′-nucleotide metabolism in human renal cortex and renal adenocarcinoma. Kidney Int 12:172–183
Schlondorff D, Weber H (1976) Cyclic nucleotide metabolism in compensatory renal hypertrophy and neonatal kidney growth. Proc Natl Acad Sci 73:524–528
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Gennari, C., Toccafondi, R., Rotella, C.M. et al. Salmon calcitonin and cGMP production by human kidney: Studies in vivo and in vitro. Calcif Tissue Int 35, 273–278 (1983). https://doi.org/10.1007/BF02405045
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DOI: https://doi.org/10.1007/BF02405045