Characteristics of nobiletin-induced effects on jejunal contractility.
Nobiletin, a citrus polymethoxylated flavone, exhibits multiple biological properties including anti-inflammatory, anti-carcinogenic, and anti-insulin resistance effects. The present study found that nobiletin exerted significant stimulatory effects on the contractility of isolated rat jejunal segments in all 6 different low contractile states, and meanwhile significant inhibitory effects in all 6 different high contractile states, showing characteristics of bidirectional regulation (BR). Nobiletin-exerted BR on jejunal contractility was abolished in the presence of c-kit receptor tyrosine kinase inhibitor imatinib or Ca(2+) channel blocker verapamil. In the presence of neuroxin tetrodotoxin, nobiletin only exerted stimulatory effects on jejunal contractility in both low and high contractile states. Hemicholinium-3 and atropine partially blocked nobiletin-exerted stimulatory effects on jejunal contractility in low-Ca(2+)-induced low contractile state. Phentolamine or propranolol or l-NG-nitro-arginine significantly blocked nobiletin-exerted inhibitory effects on jejunal contractility in high-Ca(2+)-induced high contractile state respectively. The effects of nobiletin on myosin light chain kinase (MLCK) mRNA expression, MLCK protein content, and myosin light chain phosphorylation extent were also bidirectional. In summary, nobiletin-exerted BR depends on the contractile states of rat jejunal segments. Nobiletin-exerted BR requires the enteric nervous system, interstitial cell of Cajal, Ca(2+), and myosin phosphorylation-related mechanisms.
College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, PR China.
Yong-Jian
YJ
Xiong
College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, PR China.
Da-Peng
DP
Chen
College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, PR China.
Bo-Chao
BC
Lv
College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, PR China.
Fang-Fei
FF
Liu
College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, PR China.
Li
L
Wang
College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, PR China. Electronic address: linyuandmu2008@qq.com.
Yuan
Y
Lin
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017615:Enteric Nervous System / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009219:Myosin-Light-Chain Kinase / Q000187:drug effects / Q000235:genetics; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D047309:Flavones; D018727:Muscarinic Antagonists; D013779:Tetrodotoxin; D001285:Atropine; D014700:Verapamil; C008661:nobiletin; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D002118:Calcium
Acetic acid (PubChem CID: 176); Atropine (PubChem CID: 174174); Bidirectional regulation; Ca(2+); Enteric nervous system; Hemicholinium-3 (PubChem CID: 9399); Imatinib (PubChem CID: 5291); Interstitial cell of Cajal; Jejunal contractility; Nobiletin; Nobiletin (PubChem CID: 72344); Phentolamine (PubChem CID: 5775); Propranolol (PubChem CID: 4946); Tetrodotoxin (PubChem CID: 11174599); Verapamil (PubChem CID: 2520); l-NG-nitro-arginine (PubChem CID: 440005)