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Characterization of the 5‐hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureter
Author(s) -
Hernández Medardo,
Barahona María Victoria,
Simonsen Ulf,
Recio Paz,
Rivera Luis,
Martínez Ana Cristina,
GarcíaSacristán Albino,
Orensanz Luis M,
Prieto Dolores
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705019
Subject(s) - endocrinology , rauwolscine , medicine , spiperone , agonist , phentolamine , 5 ht receptor , hexamethonium , chemistry , receptor , tetrodotoxin , prazosin , guanethidine , ketanserin , contraction (grammar) , serotonin , biology , stimulation , antagonist
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. 5‐HT (0.01–10 μ M ) concentration‐dependently increased the tone of intravesical ureteral strips, whereas the increases in phasic contractions were concentration‐independent. The 5‐HT 2 receptor agonist α‐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 μ M ), a monoaminooxidase A/B activity inhibitor, produced leftward displacements of the concentration‐response curves for 5‐HT. 5‐HT‐induced tone was reduced by the 5‐HT 2 and 5‐HT 2A receptor antagonists ritanserine (0.1 μ M ) and spiperone (0.2 μ M ), respectively. However, 5‐HT contraction was not antagonized by cyanopindolol (2 μ M ), SDZ–SER 082 (1 μ M ), Y‐25130 (1 μ M ) and GR 113808 (0.1 μ M ), which are respectively, 5‐HT 1A/1B , 5‐HT 2B/2C , 5‐HT 3 , and 5‐HT 4 selective receptor antagonists. Removal of the urothelium did not modify 5‐HT‐induced contractions. Blockade of neuronal voltage‐activated sodium channels, α‐adrenergic receptors and adrenergic neurotransmission with tetrodotoxin (1 μ M ), phentolamine (0.3 μ M ) and guanethidine (10 μ M ), respectively, reduced the contractions to 5‐HT. However, physostigmine (1 μ M ), atropine (0.1 μ M ) and suramin (30 μ M ), inhibitors of cholinesterase activity, muscarinic‐ and purinergic P 2 ‐receptors, respectively, failed to modify the contractions to 5‐HT. 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.British Journal of Pharmacology (2003) 138 , 137–144. doi: 10.1038/sj.bjp.0705019