Binding of the sea anemone polypeptide BDS II to the voltage-gated sodium channel.
BDS II, a 43-residue polypeptide from the sea anemone Anemonia sulcata, is reported to have both antihypertensive and antiviral activity. This polypeptide possesses a number of sequence and structural similarities to a class of cardiotonic proteins which bind to receptor site 3 of the voltage-gated sodium channel. In contrast to these cardiostimulant proteins, which produce positive inotropic effects at concentrations of 2-15 nM, BDS II produced a weak negative inotropic effect upon isolated guinea-pig atria, with doses of 90 and 180 nM depressing contractile strength by 15 and 28%, respectively. BDS II also competed with a 125-iodine labelled derivative of AP-A (a representative of the cardiostimulant proteins) bound to sodium channels in rat brain synaptosomes. The IC50 for BDS II versus AP-A was 5.2 microM. BDS II may therefore be considered an antagonist for receptor site 3 of the voltage-gated sodium channel. Structural differences between BDS II and the agonist AP-A which may give rise to their different effects on the sodium channel are considered.
Llewellyn
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LE
School of Biochemistry, University of New South Wales, Kensington, Australia.
Norton
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D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001794:Blood Pressure / Q000502:physiology; D003064:Cnidarian Venoms / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007457:Iodine Radioisotopes; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D012615:Sea Anemones / Q000737:chemistry*; D015222:Sodium Channels / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D000959:Antihypertensive Agents; C072544:BDS II protein, Anemonia sulcata; D003064:Cnidarian Venoms; D007457:Iodine Radioisotopes; D015222:Sodium Channels