FUNCTIONAL COUPLING BETWEEN THE ACTIVE-TRANSPORT OF GLUCOSE AND THE SECRETION OF INTESTINAL NEUROTENSIN IN RATS

1. In this study, the mechanisms involved in the release of neurotensi n-like immunoreactivity (NTLI) by glucose were investigated with the i solated, vascularly perfused rat jejunoileum preparation. 2. Luminal i nfusion of glucose (1-250 mM) produced a sharp and sustained release o f NTLI in the intestinal venous effluent. The first significant respon se was observed with 5 mM glucose and the release reached a maximum un der 250 mM glucose with a plateau secretion at 500% of basal. 3. There was no significant difference in the ability of galactose and 3-O-met hylglucose to release NTLI when compared to glucose, but alpha-methylg lucose, mannose, 2-deoxyglucose and fructose did not stimulate NTLI re lease. 4. Luminal infusion of 5 mM phloridzin reduced the glucose-indu ced release of NTLI by 90%. Intra-arterial infusion of glucose (25 mM) or of phloretin (20 muM) had no significant effect on the glucose-evo ked NTLI secretion. 5. Intra-arterial infusion of ouabain (1 mM) produ ced a dramatic increase (at about 1500% of basal) in portal NTLI altho ugh it drastically reduced intestinal absorption of glucose. 6. Intra- arterial infusion of tetrodotoxin (1 muM), atropine (10 muM), verapami l (50 muM) or nifedipine (50 muM) did not modify the glucose-induced N TLI secretion. 7. Intra-arterial infusion of forskolin (2-20 muM) evok ed a prompt and well-sustained secretion of NTLI which was increased t o a mean value of 800% of basal with the highest dose tested. 3-Isobut yl-1-methylxanthine (IBMX, 10-100 muM) also stimulated the secretion o f NTLI (maximal increase at 725% of basal at 100 muM). In contrast, in tra-arterial infusion of 4-beta-phorbol 12-myristate, 13-acetate (PMA, 0.05-0.5 muM) had no effect on NTLI release. 8. IBMX (10-100 muM) syn ergistically enhanced NTLI responses induced by 250 mM glucose; the in tegrated response of NTLI release was 3- to 5-fold higher than the sum of individual responses produced by the same stimulants given separat ely. 9. It is concluded that the carbohydrate-induced NTLI release is related to the active, sodium-dependent hexose transport, but not to t he carbohydrate catabolic pathway. Furthermore, the intramural nerves and L-type calcium channels are not involved in the glucose-induced NT LI secretion. Finally, the secretory activity of the intestinal N cell seems to be mainly stimulated through a cAMP-dependent pathway.