TACHYKININERGIC EXCITATORY NEUROTRANSMISSION IN THE PIG INTRAVESICAL URETER

Abstract

The present investigation was designed to study the role played by neurokinin A (NKA) in the non adrenergic non cholinergic (NANC) neurotransmission of the pig intravesical ureter. We used immunohistochemical techniques to evidence the distribution of NKA-immunoreactive (NKA-IR) fibers in the pig intravesical ureter. We have also performed isolated organ bath experiments to release endogenous tachykinins from ureteral nerves and to characterize the functionally active receptor through which endogenous ligands evoke contraction, and to show the effect of exogenous tachykinins on intravesical ureteral smooth muscle. NKA-IR fibers were found penetrating through ureteral adventitia and 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 GR 94800 (3 x 10-8 M), sensory neurotoxin and NK2 receptor antagonist, respectively. Contractions 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. These results suggest that tachykinins, especially NKA, released from capsaicin-sensitive primary afferents, are involved in the NANC excitatory 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 extravasation or ganglionar transmission.