Intracellular calcium mobilization as a target for the spasmolytic action of scopoletin.
The coumarin scopoletin was isolated in a pure form from the roots of Brunfelsia hopeana Benth. (Solanaceae). In isolated rat aortic rings, scopoletin (26-520 microM) inhibited to approximately the same extent the contractions induced by a variety of substances, including phenylephrine, potassium chloride, serotonin and PGF(2) (alpha). The effect of the coumarin on phenylephrine-induced contractions was not affected by endothelium removal or NO-synthase blockade by L-NAME (100 microM). Scopoletin (78 - 590 microM) antagonized in a concentration-dependent manner (IC(50) = 300 +/- 20 microM, n = 5), transient contractions in Ca(2+)-free media induced by noradrenaline, but not those induced by caffeine. Also, scopoletin did not interfere with the refilling of noradrenaline-sensitive intracellular calcium stores. It is suggested that the non-specific spasmolytic action of scopoletin can be attributed, at least in part, to its ability to inhibit the intracellular calcium mobilization from the noradrenaline-sensitive stores.
Oliveira
E J
EJ
Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, 58051-970 João Pessoa, PB, Brazil.
Romero
M A
MA
Silva
M S
MS
Silva
B A
BA
Medeiros
I A
IA
D000818:Animals; D001011:Aorta; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015237:Dinoprost / Q000819:agonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D010656:Phenylephrine / Q000819:agonists; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D011189:Potassium Chloride / Q000819:agonists; D051381:Rats; D017208:Rats, Wistar; D012603:Scopoletin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D019657:Solanaceae / Q000737:chemistry*; D014661:Vasoconstriction / Q000187:drug effects
D003374:Coumarins; D010276:Parasympatholytics; D010936:Plant Extracts; D010656:Phenylephrine; D012701:Serotonin; D002110:Caffeine; D011189:Potassium Chloride; D015237:Dinoprost; D012603:Scopoletin; D002118:Calcium; D009638:Norepinephrine