Peptidyl-urea based inhibitors of soluble epoxide hydrolases.

We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (K(I)=15nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.

P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin.

Objectives: The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex.

Capsaicin receptor VR1 and ATP purinoceptor P2X3 in painful and nonpainful human tooth pulp.

Aims: To investigate the levels of the capsaicin or vanilloid receptor-1 (VR1) and the ATP-gated purinoceptor P2X3 in painful and nonpainful human tooth pulps.

Methods: Immunohistochemistry with specific antibodies and image analysis was used to quantify VR1- and P2X3-positive nerve fibers in painful (n = 13) and nonpainful (n = 33) human tooth pulps, and VR1 immunoreactivity was compared with immunoreactivity for the structural neuronal marker peripherin.

Results: Strong VR1-like immunoreactivity was documented for the first time in dental pulp neurons.