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- Title
5-hydroxytryptamine induced relaxation in the pig urinary bladder neck.
- Authors
Recio, Paz; Barahona, María Victoria; Orensanz, Luis M.; Bustamante, Salvador; Martínez, Ana Cristina; Benedito, Sara; García-Sacristán, Albino; Prieto, Dolores; Hernández, Medardo; Barahona, María Victoria; Martínez, Ana Cristina; García-Sacristán, Albino; Hernández, Medardo
- Abstract
Background and purpose: 5-Hydroxytryptamine (5-HT) is one of the inhibitory mediators in the urinary bladder outlet region. Here we investigated mechanisms involved in 5-HT-induced relaxations of the pig bladder neck. Experimental approach: Urothelium-denuded strips of pig bladder were mounted in organ baths for isometric force recordings of responses to 5-HT and electrical field stimulation (EFS). Key results: After phenylephrine-induced contraction, 5-HT and 5-HT receptor agonists concentration-dependently relaxed the preparations, with the potency order: 5-carboxamidotryptamine (5-CT) > 5-HT = RS67333 > (±)-8-hydroxy-2-dipropylaminotetralinhydrobromide > m-chlorophenylbiguanide > α-methyl-5-HT > ergotamine. 5-HT and 5-CT relaxations were reduced by the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulphonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride and potentiated by (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide dihydrochloride (WAY 100135) and cyanopindolol, 5-HT1A and 5-HT1A/1B receptor antagonists respectively. Inhibitors of 5-HT1B/1D, 5-HT2, 5-HT2B/2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT6 receptors failed to modify 5-HT responses. Blockade of monoamine oxidase A/B, noradrenergic neurotransmission, α-adrenoceptors, muscarinic and purinergic receptors, nitric oxide synthase, guanylate cyclase and prostanoid synthesis did not alter relaxations to 5-HT. Inhibitors of Ca2+-activated K+ and ATP-dependent K+ channels failed to modify 5-HT responses but blockade of neuronal voltage-gated Na+-, Ca2+- and voltage-gated K+ (Kv)-channels potentiated these relaxations. Adenylyl cyclase activation and cAMP-dependent protein kinase (PKA) inhibition potentiated and reduced, respectively, 5-HT-induced responses. Under non-adrenergic, non-cholinergic, non-nitrergic conditions, EFS induced neurogenic, frequency-dependent, relaxations which were resistant to WAY 100135 and cyanopindolol. Conclusions and implications: 5-HT relaxed the pig urinary bladder neck through muscle 5-HT7 receptors linked to the cAMP-PKA pathway. Prejunctional 5-HT1A receptors and Kv channels modulated 5-HT-induced relaxations whereas postjunctional K+ channels were not involved in such responses. 5-HT7 receptor antagonists could be useful in the therapy of urinary incontinence produced by intrinsic sphincter deficiency.
- Subjects
SEROTONIN; URINARY organs; LABORATORY swine; MONOAMINE oxidase; AMINE oxidase; POTASSIUM metabolism; BLADDER physiology; IN vitro studies; BLADDER; MUSCLE contraction; SWINE; CELLULAR signal transduction; ELECTRIC stimulation; TRANSFERASES; SEROTONIN agonists; ANIMALS; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2009, Vol 157, Issue 2, p271
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2009.00144.x