Vascular L-type Ca²âº channel blocking activity of sulfur-containing indole alkaloids from Glycosmis petelotii.
J Nat Prod
; 77(7): 1586-93, 2014 Jul 25.
Article
en En
| MEDLINE
| ID: mdl-24949913
ABSTRACT
In the search for novel natural compounds endowed with potential antihypertensive activity, a new sulfur-containing indole alkaloid, N-demethylglypetelotine (2), and its known analogue glypetelotine (1), were isolated from the leaves of Glycosmis petelotii. Their structures were established on the basis of spectroscopic evidence. The two alkaloids were assessed for vasorelaxing activity on rat aorta rings and for L-type Ba(2+) current [I(Ba(L))] blocking activity on single myocytes isolated from rat tail artery. Both glypetelotine and N-demethylglypetelotine inhibited phenylephrine-induced contraction with IC50 values of 20 and 50 µM, respectively. The presence of endothelium did not modify their spasmolytic effect. Neither glypetelotine nor N-demethylglypetelotine affected Ca(2+) release from the sarcoplasmic reticulum induced by phenylephrine. The spasmolytic effect of glypetelotine increased with membrane depolarization. In the presence of 60 mM K(+), both compounds inhibited, in a concentration-dependent manner, the contraction induced by cumulative addition of Ca(2+), this inhibition being inversely related to Ca(2+) concentration. Glypetelotine and, less efficiently N-demethylglypetelotine, inhibited I(Ba(L)), the former compound also affecting I(Ba(L)) kinetics. In conclusion, glypetelotine is a novel vasorelaxing agent which antagonizes L-type Ca(2+) channels.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Azufre
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Vasodilatadores
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Bloqueadores de los Canales de Calcio
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Canales de Calcio Tipo L
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Rutaceae
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Alcaloides Indólicos
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Músculo Liso Vascular
Límite:
Animals
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Nat Prod
Año:
2014
Tipo del documento:
Article