Substance P action on phosphoinositides in guinea-pig intestinal muscle: a possible transduction mechanism?
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The effect of substance P on the metabolism of membrane phosphoinositides and the possible role of this effect in the contractile response to substance P was investigated in longitudinal muscle strips obtained from the guineapig small intestine and prelabelled with [3H] inositol.
Substance P (2.2 μM) failed to change significantly the tissue content of phosphoinositides but caused an accumulation of their water-soluble hydrolysis products, inositol bis-phosphate (InsP2) and inositol monophosphate (InsP). These experiments were carried out in the presence of Li+ (12 mM), since only under these conditions could an accumulation of InsP2 be observed.
The rate at which InsP2 and InsP accumulated was highest during the first 0.5 min of exposure to substance P (2.2 μM) and then decreased rapidly. Thus, the rate of inositol phosphate accumulation paralleled the time course of the contractile response to substance P.
The magnitude of inositol phosphate accumulation was related to the concentration of substance P (22 nM-22 μM).
The substance P-induced accumulation of InsP2 and InsP was not reduced when muscle strips had been incubated in Ca2+-free medium, for a time period sufficient to deplete the intracellular Ca2+ store which can be released by substance P, or in Ca2+-free medium containing high [K+].
These findings are compatible with the concept that hydrolysis of membrane phosphoinositides is a mechanism than links substance P receptor activation to contraction but further work is needed to establish a causal relationship.
Key wordsSubstance P Phosphoinositide metabolism Intestinal smooth muscle Stimulus-effect coupling
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