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Inhibition by Clonidine of the Carbachol-Induced Tension Development and Nonselective Cationic Current in Guinea Pig Ileal Myocytes

 SeungSoo Chung  ;  SeongChun Kwon  ;  YunSuk Kim  ;  DuckSun Ahn  ;  YoungHo Lee  ;  TaickSang Nam 
 Japanese Journal of Pharmacology, Vol.87(2) : 125-133, 2001 
Journal Title
 Japanese Journal of Pharmacology 
Issue Date
Adrenergic alpha-Agonists/pharmacology* ; Adrenergic alpha-Antagonists/pharmacology ; Animals ; Calcium Channels/drug effects ; Carbachol/pharmacology* ; Clonidine/pharmacology* ; Female ; Guinea Pigs ; Ileum/cytology ; Ileum/drug effects ; Ileum/physiology* ; Imidazoline Receptors ; In Vitro Techniques ; Ion Channels/antagonists & inhibitors* ; Male ; Muscarinic Agonists/pharmacology* ; Muscle Contraction/drug effects ; Muscle, Smooth/cytology ; Muscle, Smooth/drug effects ; Muscle, Smooth/physiology* ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated/antagonists & inhibitors ; Receptors, Adrenergic, alpha-2/drug effects ; Receptors, Drug/drug effects
Gastrointestinal smooth muscle ; Carbachol ; Cationic current ; Clonidine ; Imidazoline
Effects of clonidine, an imidazoline derivative as well as α2-adrenoceptor agonist, on carbachol (CCh)-evoked contraction in guinea pig ileal smooth muscle were studied using isometric tension recording. To investigate the cellular mechanisms of the inhibitory effect of clonidine, its effects on CCh-evoked nonselective cationic current (ICCh), voltage-dependent Ca2+ current (ICa) and voltage-dependent K+ current (IK) was also studied using patch-clamp recording techniques in single ileal cells. Clonidine inhibited the contraction evoked by CCh (1 μM) in a concentration-dependent manner with an IC50 valve of 61.7 ± 2.5 μM. High K+ (40 mM)-evoked contraction was only slightly inhibited even when clonidine was used at 300 μM. Externally applied clonidine inhibited ICCh dose-dependently with an IC50 of 42.0 ± 2.6 μM. When applied internally via patch pipettes, clonidine was without effect. An ICCh-like current induced by GTPγS was also inhibited by bath application of clonidine. None of KU14R and BU224, both imidazoline receptor blockers, and yohimbine, an α2-adrenergic blocker, significantly affects the inhibitory effect of clonidine on ICCh. Clonidine (300 μM) only slightly decreased membrane currents flowing through voltage-gated Ca2+ channels or K+ channels. These data indicate that clonidine relaxes smooth muscle contraction produced by muscarinic receptor activation and suggest that the effect of clonidine seems due mainly to inhibition of ICCh via acting directly on the involved cationic channel.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Nam, Taick Sang(남택상)
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
Lee, Young Ho(이영호) ORCID logo https://orcid.org/0000-0002-5749-1045
Chung, Seung Soo(정승수) ORCID logo https://orcid.org/0000-0002-3119-9628
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