PHOSPHOINOSITIDE METABOLISM IN INTESTINAL SMOOTH-MUSCLE - PREFERENTIAL PRODUCTION OF INS(1,4,5)P3 IN CIRCULAR MUSCLE-CELLS

The pattern of inositol phospholipid metabolism in response to stimulation by contractile agonists was examined in muscle cells isolated separately from circular and longitudinal muscle layers of guinea pig intestine. Addition of cholecystokinin octapeptide (CCK-8) to circular muscle cells caused a prompt decrease in phosphatidylinositol 4,5-bisphosphate (PtdInsP2) (50 +/- 6%) and PtdInsP (38 +/- 9%), which reached a nadir in 15 s. Addition of CCK-8 to longitudinal muscle cells caused a decrease in PtdInsP only (42 +/- 6%); PtdInsP2 levels, which were three times lower in this cell type, did not change throughout the period of stimulation. Hydrolysis of PtdInsP2 in circular muscle cells was accompanied by a concentration-dependent increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]; the maximal increase was 10 to 16 times greater in circular muscle cells as measured by radioreceptor assay and by ion-exchange chromatography. The small amounts of InsP3 produced in longitudinal muscle cells did not result from more rapid degradation, since the rates of disappearance of exogenous Ins(1,4,5)P3 in both cell types were similar. Within 5 s after addition of CCK-8, InsP3 comprised 73 +/- 5% of total inositol phosphates produced in circular muscle cells and 2.0 +/- 0.2% in longitudinal muscle cells. These divergent patterns indicate that inositol phospholipid metabolism is channeled toward generation of InsP3 in circular muscle cells only; the metabolic pattern in these cells parallels the selective presence of high-affinity InsP3 receptors and the pattern of intracellular Ca2+ mobilization.