title: Inhibitory effect of schisandrin on spontaneous contraction of isolated rat colon.
abstract: This study examined the effect of schisandrin, one of the major lignans isolated from Schisandra chinensis, on spontaneous contraction in rat colon and its possible mechanisms. Schisandrin produced a concentration-dependent inhibition (EC₅₀=1.66 μM) on the colonic spontaneous contraction. The relaxant effect of schisandrin could be abolished by the neuronal Na+ channel blocker tetrodotoxin (1 μM) but not affected by propranolol (1 μM), phentolamine (1 μM), atropine (1 μM) or nicotine desensitization, suggesting possible involvement of non-adrenergic non-cholinergic (NANC) transmitters released from enteric nerves. N(ω)-nitro-l-arginine methyl ester (100-300 μM), a nitric oxide synthase inhibitor, attenuated the schisandrin response. The role of nitric oxide (NO) was confirmed by an increase in colonic NO production after schisandrin incubation, and the inhibition on the schisandrin responses by soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-α]-quinoxalin-1-one (1-30 μM). Non-nitrergic NANC components may also be involved in the action of schisandrin, as suggested by the significant inhibition of apamin on the schisandrin-induced responses. Pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (100 μM), a selective P2 purinoceptor antagonist, markedly attenuated the responses to schisandrin. In contrast, neither 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A₁ receptors, nor chymotrypsin, a serine endopeptidase, affected the responses. All available results have demonstrated that schisandrin produced NANC relaxation on the rat colon, with the involvement of NO and acting via cGMP-dependent pathways. ATP, but not adenosine and VIP, likely plays a role in the non-nitrergic, apamin-sensitive component of the response.
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Yang
authors.forename: Paul S P
authors.initials: PS
authors.lastname: Ip
authors.forename: John H K
authors.initials: JH
authors.lastname: Yeung
authors.forename: Chun-Tao
authors.initials: CT
authors.lastname: Che
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D044682:Colon, Ascending / Q000187:drug effects* / Q000601:surgery; D006152:Cyclic GMP / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation; D009569:Nitric Oxide / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D058914:Purinergic Antagonists / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol / Q000037:antagonists & inhibitors; D032141:Schisandra / Q000737:chemistry; D013779:Tetrodotoxin / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: C514222:(2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline); D018674:Adrenergic Antagonists; D001593:Benzyl Compounds; D034242:Cyclooctanes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D017705:Lignans; D010936:Plant Extracts; D011083:Polycyclic Compounds; D058914:Purinergic Antagonists; D044006:Receptors, Epoprostenol; D014970:Xanthines; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D009569:Nitric Oxide; D013779:Tetrodotoxin; D011732:Pyridoxal Phosphate; D001285:Atropine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011433:Propranolol; C011105:schizandrin; D006152:Cyclic GMP; D010646:Phentolamine