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Properties of receptors for neurotoxic phospholipases A2 in different tissues

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Abstract

A radioiodinated derivative of OS2 (125I−OS2), a neurotoxic monochain phospholipase A2 isolated from taipan venom, was previously found to bind to a specific brain membrane receptor with very high affinity.125I−OS2 is now used to identify the properties of neurotoxic phospholipase receptors in other tissues. Heart, skeletal muscle, kidney, lung, liver, pancreas, and smooth muscle membranes also contain high-affinity binding sites for toxic phospholipases A2. In most tissues, two different types of receptor sites have been characterized for125I−OS2 with Kd1 and Kd2 values in the 1–5 pM and the 10–50 pM range respectively. Whereas all receptors are similar in the different tissues in terms of their affinity for125I−OS2, maximal binding site capacities were very different, varying from 1.4 pmol/mg of protein in brain to 0.01 pmol/mg of protein in pancreaas. In brain, heart, and skeletal muscle, receptor densities vary with in vivo development. Affinity labeling experiments have identified the subunit composition of OS2 receptors and indicated that these receptors do not have identical structures in the different tissues. Binding competition studies with OS2 and other toxic phospholipases showed tissue-dependent pharmacological profiles. All these results taken together suggest the existence of a family of receptors for neurotoxic phospholipases.

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Abbreviations

PLA2 :

phospholipase A2

DSS:

suberic acid bis-N-hydroxysuccinimide ester

EDTA:

ethylenediaminetetraacetic acid

Hepes:

4-(2-hydroxyethyl)1-piperazine ethanesulfonic acid

SDS:

sodium dodecyl sulfate

OS1 :

Oxyuranus scutellatus scutellatus toxin 1

OS2 :

Oxyuranus scutellatus scutellatus toxin 2

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Authors and Affiliations

  1. Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Sophia Antipolis, 06560, Valbonne, France

    Gérard Lambeau, Michel Lazdunski & Jacques Barhanin

Authors
  1. Gérard Lambeau
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  2. Michel Lazdunski
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  3. Jacques Barhanin
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Special issue dedicated to Dr. Lawrence Austin.

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Lambeau, G., Lazdunski, M. & Barhanin, J. Properties of receptors for neurotoxic phospholipases A2 in different tissues. Neurochem Res 16, 651–658 (1991). https://doi.org/10.1007/BF00965551

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