Abstract
The reports that the sulfonylurea compounds have a vasopressin-like action in some patients with diabetes insipidus (DI) and NAHONEY and GOODMAN's observations of benefit in one patient with hypodipsia led us to a trial in three children with both deficiencies. Hitherto extraordinarily difficult management problems, these children have shown restoration of homeostatically appropriate thirst and facultative urinary concentrating ability during chlorpropamide (CPM) treatment.
Observations to provide insight into the mechanism of these clinical effects were as follows: much as in total diabetes mellitus, the sulfonylureas were without benefit in total vasopressin lack (Brattleboro rats) and in clinical nephrogenic. DI Sulfonylureas, while inactive alone, augumented vasopressin stimulated water flux across toad bladder. Water flux induced by cyclic 3′,5′ AMP was not increased suggesting the compounds act neither by augmenting the influence of second messenger nor by phosphodiesterase inhibition. CPM treatment increased and prolonged parathyroid hormone provoked urinary excretion of cyclic 3′,5′ AMP in two patients with pseudohypoparathyroidism much as it extended and intensified antidiuresis due to exogenous vasopressin in water loaded normals.
The observations support the hypothesis that sulfonylureas act by amplifying the cyclic 3′,5′ AMP signal generated by hormones at their specific target tissues, possibly including CNS, where second messenger concentrations are high. If correct, the amplifier hypothesis implies extend applicability of sulfonylureas and their congeners in restoring homeostasis in states of attenuated endocrine secretion.
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Bode, H., Harley, B., Spiegel, A. et al. Sulfonylureas Amplify Cyclic 3′, 5′ AMP Mediated Hormone Action. Pediatr Res 4, 458 (1970). https://doi.org/10.1203/00006450-197009000-00097
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DOI: https://doi.org/10.1203/00006450-197009000-00097