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On the chemistry and action of pardaxin
PRI
ON TH8 CHEMISTRY AND ACTION OF PARDABII~i
N. Primor and E. Zlotkin Department of Zoology, The Hebrew University of Jerusalem, Jerusalem, Israel .
The finding of CLABiC and CHAD (1973) that the Red Sea flatfish Pardachirus marmoratus possesses a fish lethal (ichthyotozic) secretion (PMC) has stímu].ated the study of its chemistry and pharmacology . The usage of column chromatography enabled the purification of the main ichthyotoaic factor named Pardaxin . It is a single chained acidic polypeptide composed of 162 amino acids with a M.W . of about 17,000 and a very unique amino acid composition (PR]liOR et al ., 1978) . The findings concerning the pharmacology of PMC and Pardazia can be devíded into two basic categories : Those indicating their (a) structural effects to biological membranes and (b) direct involvement is processes related to ion transport . Structural damage of bio logical membranes was ezpressed in (1) The direct hemolysie of human erythrocytes (PR13t0R and ZLOTR]71, 1975) and disruption of tissue cultured lymphocytes and chick embryo heart cells. (2) Histopathological changes in frog neuromuscular junctions associated to spontaneou~ depletion of transmitter (SP]:RA et al ., 1976) . (3) Transmitter release due to an effect oa presynaptic nerve terminals in an deal smooth muscle preparation (PARNESS and ZLOTR]1!I, 1976) (4) Structural damage of gills in fishes submitted to lethal and superlethal doses (PR]140R et al ., in preparation) . Most recent studies (PR]I40R et al . in preparation) concerning the ichthyotoxic mechanism of PMC and Pardaxia pointed to an interaction with processes associated to ionic transport and osmoregul.ation in fish gills. The study was performed using is vivo lethality tests and in vitro gill preparations of euryhaliae fishes preadapted to different salinities . Fish adaptation to extreme saliaities is associated to the activation of the gill oamoregulatory system including the activation of the fish gills membranel Na - R dependent ATPase (MAETZ 7:974) . Comperative studies with Ouabain and Cobra venom cardiotoxin were performed sad it has been found that (1) The gills of fishes were identified as the target organ of the íchthyotoaic action and were affected only through an external application of the toxic substances . (2) The lethal potencies of PMC and Pardaxin increased in fishes adapted to salinities above and below the isotonic level . (3) In contrast to PMC and Pardaxin the lethal effects of Ouabain and Cardiotoxin were : (a) weak upon external application (b) potent by injection and (c) independent in the salinity preadaptation of the fish . (4) When compared to Ouabaia Pardaain was found to be about three and five orders of magnitude more potent gill ATPase inhibitor in fish and crustacean preparations respectively . (5) EM studies of gills obtained from fish treated by sublethal doses of PMC revealed cytological features typical to the oamoregulatory activity of the gill epithelium (MAETZ 1974, RARNARY et al ., 1976) . It is suggested that the PMC and Pardaain induced ichtyotoxicity is due to an effect on the fish oamoregulatory mechanism. The clarification of the mode of action of the above substances may enable their employment as pharmacological tools for the study of ion transport mechanisms in cejLular physiology . MAETZ, J. (1974) In : Biochemical and Biophysical Perspectives in Marine Biology (Ed. Malins, D.C . and Sergent, I .R .) vol l, 1 . A.P . KARNARI, K.J ., K7NTER, L.B ., RINTER, W.B . and STIRL]NG, C.F . (1976) J. Ce11 .Bio1 .70,157 . PARNESS, J. and ZLOTK7N, E. (1976) Toxicon , 14, 85 . PRII~fOR, N. and ZLOTRIN, E . (1975) Toxicon , 13, 227 . PRIMOR, N. PARNESS, J . and ZLOTK]N, E . (1978) In : Toxins Animal, Plant and Microbial (Ed . Rosenberg, P .) p .539, Pergamon .
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ON TH8 CHEMISTRY AND ACTION OF PARDABII~i
N. Primor and E. Zlotkin Department of Zoology, The Hebrew University of Jerusalem, Jerusalem, Israel .
The finding of CLABiC and CHAD (1973) that the Red Sea flatfish Pardachirus marmoratus possesses a fish lethal (ichthyotozic) secretion (PMC) has stímu].ated the study of its chemistry and pharmacology . The usage of column chromatography enabled the purification of the main ichthyotoaic factor named Pardaxin . It is a single chained acidic polypeptide composed of 162 amino acids with a M.W . of about 17,000 and a very unique amino acid composition (PR]liOR et al ., 1978) . The findings concerning the pharmacology of PMC and Pardazia can be devíded into two basic categories : Those indicating their (a) structural effects to biological membranes and (b) direct involvement is processes related to ion transport . Structural damage of bio logical membranes was ezpressed in (1) The direct hemolysie of human erythrocytes (PR13t0R and ZLOTR]71, 1975) and disruption of tissue cultured lymphocytes and chick embryo heart cells. (2) Histopathological changes in frog neuromuscular junctions associated to spontaneou~ depletion of transmitter (SP]:RA et al ., 1976) . (3) Transmitter release due to an effect oa presynaptic nerve terminals in an deal smooth muscle preparation (PARNESS and ZLOTR]1!I, 1976) (4) Structural damage of gills in fishes submitted to lethal and superlethal doses (PR]140R et al ., in preparation) . Most recent studies (PR]I40R et al . in preparation) concerning the ichthyotoxic mechanism of PMC and Pardaxia pointed to an interaction with processes associated to ionic transport and osmoregul.ation in fish gills. The study was performed using is vivo lethality tests and in vitro gill preparations of euryhaliae fishes preadapted to different salinities . Fish adaptation to extreme saliaities is associated to the activation of the gill oamoregulatory system including the activation of the fish gills membranel Na - R dependent ATPase (MAETZ 7:974) . Comperative studies with Ouabain and Cobra venom cardiotoxin were performed sad it has been found that (1) The gills of fishes were identified as the target organ of the íchthyotoaic action and were affected only through an external application of the toxic substances . (2) The lethal potencies of PMC and Pardaxin increased in fishes adapted to salinities above and below the isotonic level . (3) In contrast to PMC and Pardaxin the lethal effects of Ouabain and Cardiotoxin were : (a) weak upon external application (b) potent by injection and (c) independent in the salinity preadaptation of the fish . (4) When compared to Ouabaia Pardaain was found to be about three and five orders of magnitude more potent gill ATPase inhibitor in fish and crustacean preparations respectively . (5) EM studies of gills obtained from fish treated by sublethal doses of PMC revealed cytological features typical to the oamoregulatory activity of the gill epithelium (MAETZ 1974, RARNARY et al ., 1976) . It is suggested that the PMC and Pardaain induced ichtyotoxicity is due to an effect on the fish oamoregulatory mechanism. The clarification of the mode of action of the above substances may enable their employment as pharmacological tools for the study of ion transport mechanisms in cejLular physiology . MAETZ, J. (1974) In : Biochemical and Biophysical Perspectives in Marine Biology (Ed. Malins, D.C . and Sergent, I .R .) vol l, 1 . A.P . KARNARI, K.J ., K7NTER, L.B ., RINTER, W.B . and STIRL]NG, C.F . (1976) J. Ce11 .Bio1 .70,157 . PARNESS, J. and ZLOTK7N, E. (1976) Toxicon , 14, 85 . PRII~fOR, N. and ZLOTRIN, E . (1975) Toxicon , 13, 227 . PRIMOR, N. PARNESS, J . and ZLOTK]N, E . (1978) In : Toxins Animal, Plant and Microbial (Ed . Rosenberg, P .) p .539, Pergamon .
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