Lysophosphatidylserine as histamine releaser in mice and rats

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Abstract
Lysophosphatidylserine is a specific inducer of histamine release in isolated mast cells. To determine whether a similar effect is manifestin vivo, the phospholipid was injected (1–5 mg/kg i.v.) into mice and rats. A dosedependent rise in blood histamine was observed in both animals. The several-fold increase in blood histamine occurred in the first minutes and was followed by a slower decline toward normal values. A second dose of lysophosphatidylserine was without effect. Systemic manifestations (depression, hypothermia, hypotension) were associated with the increased blood histamine level. When the tissue histamine stores accessible to lysophosphatidylserine were previously decreased by repeated phospholipid injections, no systemic symptoms occurred. Mobilization of carbohydrate reserves was also manifest during the action of lysophosphatidylserine. Prior treatment with compound 48/80 induced sustained refractoriness to lysophosphatidylserine. Structure-activity relationship demonstrated that the property to induce histamine release was linked to the structure of serine head group. Thus, other natural phospholipids or lysophospholipids were inactive. It is concluded that in analogy with the effect seenin vitro lysophosphatidylserine producesin vivo release of mast cell histamine.