Correction of polyuria by activation of adenylate cyclase in Brattleboro rats.

The diterpene forskolin has been demonstrated to activate adenylate cyclase in many tissues, independently of receptors, guanyl nucleotides or the guanine nucleotide regulatory protein. Rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) have a defect in the synthesis of vasopressin. This absence of vasopressin is reflected by polyuria and a decrease in the urinary excretion of cyclic AMP, which mediates the action of vasopressin in the epithelial cells of the collecting ducts. Treatment of Brattleboro rats or of control Long-Evans rats with forskolin in doses as low as 7 micrograms/animal produced a significant decrease in urine volume. The reduction in urinary volume was associated with a significant increase in the cyclic AMP content of renal medullary tissue. Thus, systemic activation of adenylate cyclase can correct the pathophysiological consequences of the absence of vasopressin.