COMPARATIVE EFFECTS OF TETRACYCLINES ON WATER FLOW ACROSS TOAD URINARY BLADDERS

¹ Renal-Electrolyte Sections, Departments of Medicine, Philadelphia Veterans Administration hospital and the University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania

Demeclocycline causes nephrogenic diabetes insipidus in man and inhibits antidiuretic hormone (ADH)-induced water flow (W) in toad urinary bladders. To clarify the possible mechanism for this action, the effects of five serosally applied tetracycline derivatives on ADH- and cyclic adenosine 3', 5'-monophosphate (cAMP)-induced W were studied in paired toad urinary hemibladders (Bufo marinus). Inhibition of cAMP-induced W was not clearly dose-related and did not correlate with any known physicochemical property of the tetracyclines. However, the relative inhibition of ADH-induced W by these drugs was dose-dependent, and followed the sequence: demeclocycline > doxycychine > minocycline > tetracycline > oxytetracycline. This sequence correlates exactly with the relative degree of serum protein binding of these drugs, but not with divalent cation chelation or lipid solubility, suggesting that ADH inhibition requires binding to cell membrane proteins important in ADH-induced water transport.