Salmon calcitonin and cGMP production by human kidney: studies in vivo and in vitro

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.