The mechanism of honokiol-induced and magnolol-induced inhibition on muscle contraction and Ca2+ mobilization in rat uterus.
The effects of honokiol and magnolol extracted from the Magnolia officinalis on muscular contractile responses and intracellular Ca(2+) mobilization were investigated in the non-pregnant rat uterus. Honokiol and magnolol (1-100 micromol/l) were observed to inhibit spontaneous and uterotonic agonists (carbachol, PGF(2alpha), and oxytocin)-, high K(+)-, and Ca(2+) channel activator (Bay K 8644)-induced uterine contractions in a concentration-dependent manner. The inhibition rate of honokiol on spontaneous contractions appeared to be slower than that of magnolol-induced response. The time periods that were required for honokiol and magnolol, at 100 micromol/l, to abolish 50% spontaneous contractions were approximately 6 min. Furthermore, honokiol and magnolol at 10 micromol/l also blocked the Ca(2+)-dependent oscillatory contractions. Consistently, the increases in intracellular Ca(2+) concentrations ([Ca(2+)](i)) induced by PGF(2alpha) and high K(+) were suppressed by both honokiol and magnolol at 10 micromol/l. After washout of these treatments, the rise in [Ca(2+)](i) induced by PGF(2alpha) and high K(+) was still partially abolished. In conclusion, the inhibitory effects of honokiol and magnolol on uterine contraction may be mediated by blockade of external Ca(2+) influx, leading to a decrease in [Ca(2+)](i). Honokiol and magnolol may be considered as putative Ca(2+) channel blockers and be of potential value in the treatment of gynecological dysfunctions associated with uterine muscular spasm and dysmenorrhea.
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D066298:In Vitro Techniques; D017705:Lignans; D018721:Muscarinic Agonists / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D002118:Calcium; D002217:Carbachol; D002492:Central Nervous System Depressants; D015237:Dinoprost; D005456:Fluorescent Dyes; D016257:Fura-2; D017705:Lignans; D018721:Muscarinic Agonists; D010120:Oxytocics; D010121:Oxytocin; D011189:Potassium Chloride; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols