The signaling of amitriptyline-induced inhibitory effect on electrical field stimulation response in colon smooth muscle

Autor: Tin Sandar Zaw, Uy Dong Sohn, Phyu Phyu Khin
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Colon
Amitriptyline
Muscarinic Antagonists
Antidepressive Agents
Tricyclic
In Vitro Techniques
Pharmacology
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
KATP Channels
Isometric Contraction
Internal medicine
medicine
Colon smooth muscle contraction
Prazosin
Animals
Channel blocker
Muscle Strength
Protein Kinase Inhibitors
Protein Kinase C
Guanethidine
Adrenergic Uptake Inhibitors
Dose-Response Relationship
Drug
Muscle
Smooth
General Medicine
Receptors
Muscarinic
Electric Stimulation
Potassium channel
030104 developmental biology
Chelerythrine
Endocrinology
chemistry
Type C Phospholipases
030211 gastroenterology & hepatology
Guanabenz
Gastrointestinal Motility
Ion Channel Gating
Signal Transduction
medicine.drug
Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology. 389:961-970
ISSN: 1432-1912
0028-1298
Popis: Amitriptyline, a well-known antidepressant, exerts inhibitory effect on electrically stimulated rat colon smooth muscle contraction. In this study, we investigated the signaling pathway of amitriptyline-induced inhibitory effect. Changes in isometric force of colon muscle were recorded on polygraph, and data were analyzed by measuring the inhibitory extent induced by amitriptyline. Firstly, muscles were contracted by stimulation with electric field stimulation (EFS), and then, amitriptyline was added cumulatively to determine its influence effect on EFS. Amitriptyline significantly inhibited EFS-induced contraction dose dependently. Then, the mechanism of inhibitory effect of amitriptyline was evaluated by pretreating with various antagonists such as L-NAME, methylene blue, atropine, 5-HT receptors blockers, guanethidine, prazosin, guanabenz, isoprenaline, Y27632 (Rho-kinase inhibitor), ML9 (myosin light chain kinase (MLCK) inhibitor), U73122 (PLC inhibitor), and chelerythrine (PKC inhibitor). Then, Ca(2+) channel blocker (nifedipine) and K(+)channel blockers, tetraethylammonium (TEA), 4-aminopyridine (4-AP), and glybenclamide, were used to determine the involvement of ion channels. L-NAME, guanabenz, 5HT4 receptor blocker, ML9, and Y27632 enhanced the effect of amitriptyline. Meanwhile, methylene blue, atropine, guanethidine, prazosin, methylsergide, ondansetron, U73122, and chelerythrine blocked its effect. It was also shown that nifedipine enhanced but TEA and glybenclamide blocked amitriptyline-induced inhibitory effect on EFS. Our results indicated that amitriptyline may exert inhibitory effect in response to EFS by inhibiting muscarinic receptors and then PLC-mediated PKC pathway leading to opening of ATP-sensitive potassium channel.
Databáze: OpenAIRE
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