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.
Thwaites
D T
DT
Gastrointestinal Drug Delivery Research Centre, University of Newcastle upon Tyne, U.K.
Simmons
N L
NL
Hirst
B H
BH
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