Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter

1 This study was designed to investigate the effect of 5-hydroxytryptamine (5-HT) and to characterize the 5-HT receptors involved in 5-HT responses in the pig intravesical ureter. 2 5-HT (0.01-10 microM) concentration-dependently increased the tone of intravesical ureteral strips, whereas the increases in phasic contractions were concentration-independent. The 5-HT(2) receptor agonist alpha-methyl 5-HT, mimicked the effect on tone whereas weak or no response was obtained with 5-CT, 8-OH-DPAT, m-chlorophenylbiguanide and RS 67333, 5-HT(1), 5-HT(1A), 5-HT(3) and 5-HT(4) receptor agonists, respectively. 5-HT did not induce relaxation of U46619-contracted ureteral preparations. Pargyline (100 microM), a monoaminooxidase A/B activity inhibitor, produced leftward displacements of the concentration-response curves for 5-HT. 3 5-HT-induced tone was reduced by the 5-HT(2) and 5-HT(2A) receptor antagonists ritanserine (0.1 microM) and spiperone (0.2 microM), respectively. However, 5-HT contraction was not antagonized by cyanopindolol (2 microM), SDZ-SER 082 (1 microM), Y-25130 (1 microM) and GR 113808 (0.1 microM), which are respectively, 5-HT(1A/1B), 5-HT(2B/2C), 5-HT(3), and 5-HT(4) selective receptor antagonists. 4 Removal of the urothelium did not modify 5-HT-induced contractions. Blockade of neuronal voltage-activated sodium channels, alpha-adrenergic receptors and adrenergic neurotransmission with tetrodotoxin (1 microM), phentolamine (0.3 microM) and guanethidine (10 microM), respectively, reduced the contractions to 5-HT. However, physostigmine (1 microM), atropine (0.1 microM) and suramin (30 microM), inhibitors of cholinesterase activity, muscarinic- and purinergic P(2)-receptors, respectively, failed to modify the contractions to 5-HT. 5 These results suggest that 5-HT increases the tone of the pig intravesical ureter through 5-HT(2A) receptors located at the smooth muscle. Part of the 5-HT contraction is indirectly mediated via noradrenaline release from sympathetic nerves.