Potentiation by neurotensin of carbachol-induced tension development in beta-escin-skinned smooth muscle of guinea-pig ileum

Effect of neurotensin (NT) on carbachol(CCh)-induced tension development du e to Ca2+ release from intracellular stores was investigated in beta-escin- skinned smooth muscle of guinea-pig ileum. NT (10 nM) increased the tension development in response to CCh. NT also increased the tension response to caffeine, another stored-Ca2+ releaser. NT did not exert such an effect in pertusis toxin (PTX)-treated preparations. Treatment with isoprenaline to e levate endogenous cyclic AMP levels or with dibutyryl cyclic AMP did not af fect the effect of NT. A nonpeptide NT antagonist, SR 48692, failed to bloc k the effect of NT. NT shifted the pCa-tension relationship in the lower di rection of Ca2+ concentration. NT was incapable of releasing Ca2+ from intr acellular stores. The results suggest that NT may cause an increase in Ca2 sensitivity of contractile elements to potentiate the CCh-induced tension development due to release of stored Ca2+ and that the effect is mediated b y SR 48692-insensitive NT receptors linked to a PTX-sensitive G protein whi ch works with no relation to a change in cytosolic cyclic AMP levels.