Molecular mechanism of apelin-13 regulation of colonic motility in rats
Autor: | Haixia Ren, He-Sheng Luo, Ying Wang, Lin Yan, Wenyao Shi, FangTing Yuan |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Patch-Clamp Techniques Calcium Channels L-Type Charybdotoxin Nifedipine Colon Myocytes Smooth Muscle Motility chemistry.chemical_element Calcium 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Large-Conductance Calcium-Activated Potassium Channels Rats Wistar Apelin receptor Pharmacology Apelin Receptors Voltage-dependent calcium channel Dose-Response Relationship Drug Apelin Cell biology Electrophysiology 030104 developmental biology Mechanism of action chemistry Tetrodotoxin Intercellular Signaling Peptides and Proteins medicine.symptom Gastrointestinal Motility 030217 neurology & neurosurgery Muscle Contraction |
Zdroj: | European journal of pharmacology. 904 |
ISSN: | 1879-0712 |
Popis: | Apelin is a novel neuropeptide identified as the endogenous ligand for the apelin receptor. Apelin and its receptor are widely distributed in the gastrointestinal tract. Studies have reported that apelin-13 is involved in modulating gastrointestinal motility; however, the evidence is insufficient and the relevant mechanism is still not fully clear. Consequently, our study designed to explore the effect induced by exogenous apelin-13, to analyze the mechanism of action in isolated rat colons and colonic smooth muscle cells. The spontaneous contractions of colonic smooth muscle strips from rat were measured in an organ bath system. L-type calcium currents and large conductance Ca2+-activated K+ (BKCa) currents in rat colonic smooth muscle cells were investigated using the electrophysiological patch-clamp technique. Apelin-13 decreased the spontaneous contractile activity of colonic smooth muscle strips in a dose-dependent manner, and the inhibitory effect was not abolished by tetrodotoxin. The electrophysiological recordings revealed that apelin-13 reduced the crest currents of L-type calcium in a concentration-dependent manner in colonic smooth muscle cells at the test potential of 0 mV. Moreover, apelin-13 moved the current-voltage (I–V) curves of L-type calcium channels upward, but did not change their contour. Furthermore, the characteristics of L-type calcium channels with steady-state activation and steady-state inactivation were not significantly changed. Similarly, application of apelin-13 also significantly decreased BKCa currents in a concentration-dependent manner. In conclusion, apelin-13 inhibited the spontaneous contractile activity of isolated rat colons via the suppression of L-type calcium channels and BKCa channels in colonic smooth muscle cells. |
Databáze: | OpenAIRE |
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