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 neurotensin-like immunoreactivity (NTLI) by glucose were investigated with the isolated, vascularly perfused rat jejunoileum preparation. 2. Luminal infusion of glucose (1-250 mM) produced a sharp and sustained release of NTLI in the intestinal venous effluent. The first significant response was observed with 5 mM glucose and the release reached a maximum under 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-methylglucose to release NTLI when compared to glucose, but alpha-methylglucose, mannose, 2-deoxyglucose and fructose did not stimulate NTLI release. 4. Luminal infusion of 5 mM phloridzin reduced the glucose-induced release of NTLI by 90%. Intra-arterial infusion of glucose (25 mM) or of phloretin (20 microM) had no significant effect on the glucose-evoked NTLI secretion. 5. Intra-arterial infusion of ouabain (1 mM) produced a dramatic increase (at about 1500% of basal) in portal NTLI although it drastically reduced intestinal absorption of glucose. 6. Intra-arterial infusion of tetrodotoxin (1 microM), atropine (10 microM), verapamil (50 microM) or nifedipine (50 microM) did not modify the glucose-induced NTLI secretion. 7. Intra-arterial infusion of forskolin (2-20 microM) evoked a prompt and well-sustained secretion of NTLI which was increased to a mean value of 800% of basal with the highest dose tested. 3-Isobutyl-1-methylxanthine (IBMX, 10-100 microM) also stimulated the secretion of NTLI (maximal increase at 725% of basal at 100 microM). In contrast, intra-arterial infusion of 4-beta-phorbol 12-myristate, 13-acetate (PMA, 0.05-0.5 microM) had no effect on NTLI release. 8. IBMX (10-100 microM) synergistically enhanced NTLI responses induced by 250 mM glucose; the integrated response of NTLI release was 3- to 5-fold higher than the sum of individual responses produced by the same stimulants given separately. 9. It is concluded that the carbohydrate-induced NTLI release is related to the active, sodium-dependent hexose transport, but not to the carbohydrate catabolic pathway. Furthermore, the intramural nerves and L-type calcium channels are not involved in the glucose-induced NTLI secretion. Finally, the secretory activity of the intestinal N cell seems to be mainly stimulated through a cAMP-dependent pathway.
Dakka
T
T
Institut National de la Santé et de la Recherche Médicale, U 45, Hôpital Edouard Herriot, Lyon, France.
Cuber
J C
JC
Chayvialle
J A
JA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001693:Biological Transport, Active / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D009496:Neurotensin / Q000276:immunology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009496:Neurotensin; D013779:Tetrodotoxin; D010042:Ouabain; D001285:Atropine; D000242:Cyclic AMP; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D010693:Phloretin; D015056:1-Methyl-3-isobutylxanthine