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.
Hernández
Medardo
M
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. medardo@vet.ucm.es
Barahona
María Victoria
MV
Simonsen
Ulf
U
Recio
Paz
P
Rivera
Luis
L
Martínez
Ana Cristina
AC
García-Sacristán
Albino
A
Orensanz
Luis M
LM
Prieto
Dolores
D
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D019459:Urothelium / Q000187:drug effects / Q000502:physiology
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D014363:Tryptamines; D016713:Ritanserin; D012701:Serotonin; C030820:tryptamine; D013779:Tetrodotoxin; D013134:Spiperone; D006145:Guanethidine