Thyrotropin-releasing hormone (TRH) uptake in intestinal brush-border membrane vesicles: comparison with proton-coupled dipeptide and Na(+)-coupled glucose transport.
The mechanism of thyrotropin-releasing hormone (pGlu-His-Pro-NH2; TRH) uptake across the luminal membrane of intestinal enterocytes was investigated using brush-border membrane vesicles (BBMV) from rabbit duodenum and jejunum and rat upper small intestine. [14C]Glucose accumulated within the intestinal vesicles (at 10 sec), in the presence of an inwardly directed Na+ gradient, 7- to 14-fold higher than equilibrium values (65 min). The vesicles also accumulated the dipeptide [14C]Gly-Sar. Dipeptide uptake was greatest in the presence of both an inwardly directed proton gradient and an inside negative membrane potential. The H(+)-dependent Gly-Sar transport was not affected by the presence of an excess (46-fold) of cold TRH. In contrast to the observations with glucose and Gly-Sar, the uptake of [3H]TRH after 10 or 60 sec (in each of the vesicle preparations) was not enhanced by either Na+ or H+ gradient conditions. The absence of vesicular accumulation of TRH was not due to peptide hydrolysis. For example, after a 60-sec incubation with rabbit jejunal BBMV no degradation of the tripeptide was evident. After 65 min, 6% of [3H]TRH had undergone degradation, by deamidation, to form TRH-OH. These studies provide no evidence for the oral absorption of TRH by a Na(+)- or H(+)-dependent carrier system in the brush-border membrane. Previous observations of TRH absorption in vivo may be accounted for by passive absorption of the peptide combined with its relative resistance to luminal hydrolysis.
Gastrointestinal Drug Delivery Research Centre, University of Newcastle upon Tyne, U.K.
D T
DT
Thwaites
N L
NL
Simmons
B H
BH
Hirst
D000818:Animals; D001692:Biological Transport; D004151:Dipeptides / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D011522:Protons; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism / Q000493:pharmacokinetics*
D004151:Dipeptides; D009004:Monosaccharide Transport Proteins; D011522:Protons; D013973:Thyrotropin-Releasing Hormone; D012964:Sodium; D005947:Glucose