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.
Sobol
C V
CV
Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of Russia, St. Petersburg. Sobol@IEF.SPB.SU
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011896:Rana temporaria; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014684:Venae Cavae
C101544:MD1; D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D003035:Cobalt; D004533:Egtazic Acid; D011189:Potassium Chloride; D002118:Calcium