V. Polyphosphoinositide breakdown as the initiating reaction in receptor-stimulated inositol phospholipid metabolism

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Authors

Colleges, School and Institutes

Abstract

All cell-surface receptors that bring about a rise in cytosol Ca2+ concentration upon stimulation appear also to provoke enhanced metabolism of inositol phospholipids. For many years, it has been thought that the initiating reaction in this response is phosphodiesterase-catalysed breakdown of phosphatidylinositol(PtdIns). However, recent experiments with hepatocytes, parotid gland and blowfly salivary gland have demonstrated very rapid breakdown of phosphatidyl-inositol-4, 5-bisphosphate (PtdIns4,5P2), and maybe also of PtdIns4P, in cells stimulated by Ca2+-mobilizing stimuli (V1-vasopressin, anqiotensin, α1-adrenergic, muscarinic cholinergic, substance P and 5-hydroxytryptamine). As with the disappearance of PtdIns that had been studied previously, this response is not Ca2+-mediated and shows a receptor occupation dose-response curve. The PtdIns 'breakdown' studied previously was probably utilization of PtdIns for resynthesis of polyphosphoinositides to replace the degraded PtdIns4,5P2. We suggest that the primary event in receptor-stimulated inositol phospholipid metabolism is phosphodiesterase attack upon PtdIns4,5P2 to yield 1,2-diacylglycerol and inositol-1,4,5-triphosphate, and that this is an essential coupling event in a general mechanism by which receptors mobilize Ca2+ in the cytosol of stimulated cells.

Details

Original languageEnglish
Pages (from-to)2083-2085
Number of pages3
JournalLife Sciences
Volume32
Issue number18
Publication statusPublished - 2 May 1983

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