Effects of papaya seed extract and benzyl isothiocyanate on vascular contraction.
To investigate their potentially toxic effects on mammalian vascular smooth muscle, pentane extracts of papaya seeds and the chief active ingredient in the extracts, benzyl isothiocyanate (BITC), were tested for their effects on the contraction of strips of dog carotid artery. BITC and the papaya seed extract caused relaxation when added to tissue strips that had been pre-contracted with phenylephrine (PE). Incubation of the tissue with papaya seed extract or BITC caused inhibition of contraction when the strips were subsequently contracted with KCl or PE. This relaxation and inhibition of contraction did not appear to be endothelium-dependent, as endothelium-denuded rings showed the same degree of relaxation or inhibition of contraction in response to the preparations/drugs as those with the endothelium intact. The effects of both BITC and the extract were irreversible, i.e., the tissue did not recover to normal contractile ability after extensive washing. Exposure of the tissue to the papaya seed extract caused slower relaxation of the tissue, compared to controls, both after contraction with PE and subsequent addition of carbachol (CCh), and after contraction with KCl and then washing. Calcium imaging studies using cultured endothelial cells showed strong influxes of Ca2+ into the cells in response to addition of the papaya seed extract. We conclude that these extracts, when present in high concentration, are cytotoxic by increasing the membrane permeability to Ca2+, and that the vascular effects of papaya seed extracts are consistent with the notion that BITC is the chief bio-active ingredient.
Wilson
Ruth K
RK
Smooth Muscle Research Program, Department of Medicine, HSC 4N40, McMaster University, 1200 Main Street W., L8N 3Z5, Hamilton, ON, Canada.
Kwan
Tony K
TK
Kwan
Chiu-Yin
CY
Sorger
George J
GJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D029441:Carica / Q000737:chemistry*; D002339:Carotid Arteries / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D017879:Isothiocyanates; D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride; C031403:benzyl isothiocyanate; D002217:Carbachol; D002118:Calcium