Mechanisms of vasoconstriction induced in frog vascular smooth muscle by MD1, a new biotechnological agent.

The mechanism of action of MD1, a new biotechnological radiotherapeutic agent of plant origin, on smooth muscle contraction was investigated. Contraction induced by MD1 consists of an initial dose-dependent transient phasic response (PR) (with ED50 = 0.11 +/- 0.02%, n = 4, the time of rise 15 s, onset of decay about 30 s) followed by a tonic contraction (TC) (at 10% MD1 only) with a maximum in 20 min (0.78 +/- 0.07 x the maximum contraction induced by 110 mmol/l KCl, n = 8, (TC/PR) = 0.94 +/- 0.11, n = 5). If the vessel was washed out during this maximum, the maximum tension was maintained for up to 2 h ("long-lasting" tension) and was abolished after perfusion with Ca(2+)-free EGTA solution (E) or H7 (0.05 mmol/l) solution. With solution E being applied 30 min before 10% MD1-induced contraction, TC was reduced by 92 +/- 3% (n = 4) in contrast to PR being reduced by 48 +/- 5% (n = 5). During TC, calcium appeared to penetrate into cells through receptor operated channels, since tension neither depended on verapamil (0.05 mmol/l) nor cobalt (up to 10 mmol/l). In solution H7 (with 10 min pretreatment), PR and TC were almost completely inhibited. It is proposed that MD1 activates the C-kinase branch of the calcium messenger system.