Effect of thrombin on cyclic AMP content in glomeruli isolated from rat kidney

Localized thrombin-mediated intravascular coagulation has been implicated as an important pathogenetic factor in a variety of glomerular and vascular diseases of the kidney. Recent studies indicate that glomerular function is affected by several hormonal agents which alter the cyclic AMP or cyclic GMP content in the glomeruli. Although thrombin has been shown to affect several metabolic processes in other cellular systems the possibility that thrombin may cause a reduction in glomerular function by altering cyclic nucleotide metabolism has not been previously considered. We therefore examined the effect of thrombin on the cyclic AMP and cyclic GMP content in glomeruli isolated from rat renal cortex. Thrombin caused a dose dependent (0.01 to 1 U/ml) increase in the cyclic AMP content in the glomeruli but had no effect on the cyclic GMP content. The effect was first observed at 30 seconds and reached a peak at five minutes. Tubules isolated from the same rats had no response to thrombin. The glomerular cyclic AMP response to thrombin inactivated with diisopropylfluorophosphate was markedly impaired, indicating the requirement for the protease activity of thrombin for the observed effect. Thrombin did not affect the cyclic AMP phosphodiesterase activity in glomeruli. Thrombin-mediated increase in glomerular cyclic AMP may play an important role in the reduction in glomerular function that is observed in a variety of glomerular and vascular renal diseases in which intravascular coagulation plays a prominent role.