Inositol 1,4,5-trisphosphate mimics muscarinic response in Xenopus oocytes

Abstract

The enhanced metabolism of phosphoinositides, which is associated with a wide variety of stimuli and physiological responses, has been studied intensively. Berridge and his collaborators^1–3 demonstrated that the first measurable reaction following cell membrane receptor activation is a rapid hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂), and that the product of this reaction, inositol 1,4,5-trisphosphate (Ins(1,4,5)P₃), could cause a release of non-mitochondrial calcium. These findings have been verified in other systems^4–6. Although the relationship between the hydrolysis of PtdIns(4,5)P₂ and the mobilization of intracellular calcium was clearly demonstrated, the direct link between Ins(1,4,5)P₃ production and the physiological response was only implied. We have investigated the possibility that the intracellular release of Ins(1,4,5)P₃ mediates the muscarinic–cholinergic response is Xenopus oocytes, and we show here that intracellularly injected Ins(1,4,5)P₃ mimics the muscarinic depolarizing chloride current in Xenopus oocytes. This is the first demonstration of a direct link between phosphoinositides metabolism and a neuro-transmitter-induced physiological response.