Bombesin potentiates taurocholic acid-induced neurotensin release in rats

The hypothesis of synergistic effects between luminal stimulants and the intramural neural network in the control of intestinal neurotensin (NT) release was investigated with an isolated vascularly perfused rat jejuno-ileum. Luminal administration of low doses of taurocholic acid (TC; 1, 5, and 10 mM) provoked only a small increase in NT-like immunoreactivity (NT-LI) in the portal effluent (50%, 100%, and 130%, respectively, above basal). Increasing the concentration of TC to 20 mM induced a strong and sustained release of NT-LI (700% above basal). The arterial infusion of bombesin (BOM; 10(-9) M) induced only a transient rise in NT-LI levels (200% above basal), with a rapid return to basal values. In contrast, 10(-9) M BOM synergistically enhanced NT-LI responses induced by 10 mM TC; the integrated response of NT-LI release was 3.2-fold higher than the sum of responses to 10(-9) M BOM and 10 mM TC alone. These cooperative effects were apparent with 10(-10) M BOM and TC concentrations over the physiological range 1-10 mM. Neither tetrodotoxin (10(-6) M) nor atropine (10(-5) M) was able to modify this synergy. Substance-P and methacholine, two other NT secretagogues, did not potentiate the TC-induced NT responses. In conclusion, BOM potentiated the release of NT induced by TC, thus suggesting that bombesinergic neurons, among other stimulatory neurons of the enteric nervous system, may modulate the sensitivity of N-cells to luminal stimulants.