5-HT4 receptor agonists enhance both cholinergic and nitrergic activities in human isolated colon circular muscle
| Autor: | Olutunde Lalude, Shanmugam Vivekanandan, Gareth J. Sanger, N B Dass, Anna K. Bassil, Selim Cellek, A K John, Emma M. Jarvie, Ramkumar Thangiah |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male medicine.medical_specialty Indoles Contraction (grammar) Colon Physiology medicine.drug_class Muscle Relaxation Scopolamine 5-HT4 receptor Muscarinic Antagonists Substance P Nitric Oxide Serotonin 5-HT4 Receptor Agonists chemistry.chemical_compound Organ Culture Techniques Neurokinin-1 Receptor Antagonists Internal medicine medicine Humans Enzyme Inhibitors Aged Benzofurans Aged 80 and over Neurotransmitter Agents Prucalopride Dose-Response Relationship Drug Endocrine and Autonomic Systems Chemistry Gastroenterology Muscle Smooth Receptors Neurokinin-3 Receptors Neurokinin-2 Middle Aged Receptor antagonist Acetylcholine Electric Stimulation NG-Nitroarginine Methyl Ester Endocrinology Tetrodotoxin Cholinergic Female Muscle Contraction medicine.drug |
| Zdroj: | Neurogastroenterology and Motility. 18:853-861 |
| ISSN: | 1365-2982 1350-1925 |
| DOI: | 10.1111/j.1365-2982.2006.00810.x |
| Popis: | Previous studies have demonstrated mixed inhibitory and facilitatory effects of 5-hydroxytryptamine-4 (5-HT(4)) receptor agonists on electrical field stimulation (EFS)-induced responses in human isolated colon. Here we report three types of responses to EFS in human isolated colon circular muscle: monophasic cholinergic contraction during EFS, biphasic response (nitrergic relaxation during EFS followed by cholinergic contraction after termination of EFS) and triphasic response (cholinergic contraction followed by nitrergic relaxation during EFS and a tachykininergic contraction after EFS). The effects of two 5-HT(4) receptor agonists, prucalopride and tegaserod were then investigated on monophasic responses only. Each compound inhibited contractions during EFS in a concentration-dependent manner. In the presence of N(omega)-nitro-l-arginine methyl ester (l-NAME) however, prucalopride and tegaserod enhanced the contractions in a concentration-dependent manner. In strips where the tone was elevated with substance-P and treated with scopolamine, EFS-induced relaxations were enhanced by the two agonists. The above observed effects by the two agonists were abolished by 5-HT(4) receptor antagonist SB-204070. The two agonists did not alter the tone raised by substance-P in the presence of scopolamine and l-NAME and did not affect carbachol-induced contractions in the presence of tetrodotoxin. These results suggest that in the circular muscle of human colon, 5-HT(4) receptor agonists simultaneously facilitate the activity of neurones which release the inhibitory and excitatory neurotransmitters, nitric oxide and acetylcholine respectively. |
| Databáze: | OpenAIRE |
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