An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine.
T1R taste receptors are present throughout the gastrointestinal tract. Glucose absorption comprises active absorption via SGLT1 and facilitated absorption via GLUT2 in the apical membrane. Trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/alpha-gustducin to activate PLC beta2 and PKC betaII. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca(2+)-dependent reciprocal relationship between the H(+)/oligopeptide transporter PepT1 and apical GLUT2, reflecting the fact that trafficking of PepT1 and GLUT2 to the apical membrane is inhibited and activated by PKC betaII, respectively. Addition of L-glutamate or sucralose to a perfusate containing low glucose (20 mM) each activated PKC betaII and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide L-Phe(PsiS)-L-Ala (1 mM), while increasing apical GLUT2 and glucose absorption within minutes. Switching perfusion from mannitol to glucose (75 mM) exerted similar effects. c-glutamate induced rapid GPCR internalization of T1R1, T1R3 and transducin, whereas sucralose internalized T1R2, T1R3 and alpha-gustducin. We conclude that L-glutamate acts via amino acid and glucose via sweet taste receptors to coordinate regulation of PepT1 and apical GLUT2 reciprocally through a common enterocytic pool of PKC betaII. These data suggest the existence of a wider Ca(2+) and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC betaII and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by L-glutamate. The network may control energy supply.
Mace
Oliver J
OJ
Department of Biology (Area 3), The University of York, Heslington, York YO10 5YW, UK.
Lister
Norma
N
Morgan
Emma
E
Shepherd
Emma
E
Affleck
Julie
J
Helliwell
Philip
P
Bronk
John R
JR
Kellett
George L
GL
Meredith
David
D
Boyd
Richard
R
Pieri
Myrtani
M
Bailey
Pat D
PD
Pettcrew
Rachel
R
Foley
David
D
D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D004734:Energy Metabolism; D020895:Enterocytes / Q000187:drug effects / Q000502:physiology; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008954:Models, Biological; D000074011:Peptide Transporter 1; D010477:Perfusion; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D027981:Symporters / Q000378:metabolism
D050580:Excitatory Amino Acid Transporter 3; D051273:Glucose Transporter Type 2; D000074011:Peptide Transporter 1; D043562:Receptors, G-Protein-Coupled; C489940:Slc15a1 protein, rat; C493398:Slc1a1 protein, rat; C495683:Slc2a2 protein, rat; D027981:Symporters; C431926:taste receptors, type 1; D018698:Glutamic Acid; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D005947:Glucose; D002118:Calcium