Tachykininergic excitatory neurotransmission in the pig intravesical ureter

Purpose: The present investigation was designed to study the role played by neurokinin A (NKA) in the non adrenergic non cholinergic (NANC) neurotrans mission of the pig intravesical ureter. Materials and Methods: We used immunohistochemical techniques to evidence t he distribution of NKA-immunoreactive (NKA-IR) fibers in the pig intravesic al ureter. We have also performed isolated organ bath experiments to releas e endogenous tachykinins from ureteral nerves and to characterize the funct ionally active receptor through which endogenous ligands evoke contraction, and to show the effect of exogenous tachykinins on intravesical ureteral s mooth muscle. Results: NKA-IR fibers were found penetrating through ureteral adventitia a nd distributed in the subepithelial and muscular layers. NKA-IR fibers were not found around small arteries supplying the ureter or in the associated intramural ganglia. Electrical field stimulation (EFS, 1 ms duration, 2 to 16 Hz, 20 s trains) performed in NANC conditions evoked frequency-dependent contractions which were reduced by capsaicin (10(-5) M) and CR 94800 (3 x 10(-8) M), sensory neurotoxin and NK2 receptor antagonist, respectively. Co ntractions to EFS were abolished by tetrodotoxin (10(-6) M). Exogenous NKA and substance P (SP) induced dose-dependent contractions, characterized by an increase of the ureteral basal tone, NKA being more potent than SP. Conclusions: These results suggest that tachykinins, especially NKA, releas ed from capsaicin-sensitive primary afferents, are involved in the NANC exc itatory neurotransmission, contracting the smooth muscle via NK2 receptors activation, in the pig intravesical ureter. NKA at this level does not seem to participate in the regulation of local blood flow, plasmatic extravasat ion or ganglionar transmission.