LUMINAL BILE-SALTS AND NEUROTENSIN RELEASE IN THE ISOLATED VASCULARLYPERFUSED RAT JEJUNO-ILEUM

Bile salts in the distal small intestine are strong stimulants of neur otensin (NT) release, but the underlying mechanisms are not known. The y were investigated using an isolated vascularly perfused rat jejuno-i leum preparation. Luminal administration of crude ox bile extract (0.2 5-1.5%, wt/vol) produced a dose-dependent release of NT-like immunorea ctivity (NT-LI), with a maximal effect after infusion of 1% bile extra ct (500% of basal). Pretreatment of the 1% bile extract with the bile salt-sequestering resin cholestyramine (2%, wt/vol) abolished NT-LI re lease. Taurocholate (TC), the major bile salt in rats, dose dependentl y increased the release of NT. The maximal secretion of NT-LI was obse rved after infusion of 20 mM TC (400& of basal). Taurodeoxycholate (20 mM) was as potent as TC in stimulating NT-LI release, but the thresho ld concentration of taurodeoxycholate for NT-LI secretion was lower th an that of TC. Glycocholate and cholate were 2- to 3-fold less potent than TC in releasing NT-LI over the concentration range 5-20 mM. Lumin al infusion of oleic acid (sodium salt; 100 mM) increased by 100% the level of NT-LI in the portal effluent, whereas 20 mM oleate had no eff ect. In contrast, the micellar form of oleic acid (20 and 100 mM) in b ile extract (1%) or TC (20 mM) dose dependently reduced the release of NT-LI induced by bile extract or TC alone. Neither intraarterial tetr odotoxin (10(-6) M), EGTA (2 mM), verapamil (5 x 10(-5) M), nor atropi ne (10(-5) M) had any effect on TC-induced NT-LI release. These result s show that the tauro-conjugated forms of cholic and deoxycholic acid are strong stimulants of NT-LI release. The N-cell response is blunted when bile salts are complexed in the lumen by oleic acid. Finally, bi le salt-induced NT-LI release is not mediated by intramural nerves and is not dependent on the activation of calcium channels.