NT5E in bladder function

FASEB article: Voiding dysfunction is prevalent in aging population, and purinergic signaling plays an important role in both urinary physiology and pathophysiology. Ecto-5’-nucleotidase (Nt5e), an enzyme converting extracellular AMP to adenosine, might play a role in bladder function. However, the functional importance of this mechanism is not understood. We have studied the bladder function in Nt5e knockout (Nt5eKO) mice. Our data indicate that Nt5eKO mice exhibit a phenotype of voiding frequency and small voids with reduced bladder contractility, supporting a role for Nt5e in regulating bladder function through modulation of bladder contraction and relaxation. However, we have also discovered compensatory mechanism of other purinergic receptors and regulating enzymes, which could mitigate dysfunctions due to loss of Nt5e in the mice and imply a novel paracrine purinergic mechanism in bladder wall. A better understanding of purinergic regulation of bladder function should facilitate improved therapeutic strategies to treat patients with voiding dysfunction.