Age-Related Variations in Jejunum and Distal Colon Contractile Response to Thyrotropin-Releasing Hormone in vitro

Neonatology ◽  
1990 ◽  
Vol 58 (1) ◽  
pp. 8-15 ◽  
Author(s):  
M.M. Heitkemper ◽  
E.F. Bond
1990 ◽  
Vol 258 (3) ◽  
pp. G447-G453 ◽  
Author(s):  
E. V. O'Loughlin ◽  
D. M. Hunt ◽  
D. Kreutzmann

Postnatal changes in adrenal gluco- and mineralocorticoid secretion and colonic sodium and chloride transport were examined. New Zealand White rabbits, age 10-14, 18-22, and 25-30 days, and adult animals (6-10 wk) were studied. Serum cortisol, corticosterone, aldosterone, and mucosal Na(+)-K(+)-ATPase activities were measured in each age group. Transport studies were performed in vitro under short-circuited conditions in distal colon at all age groups and in proximal colon in days 10-14 and 18-22 and in adult animals. Serum glucocorticoids varied little until after day 30 when they rose to adult levels. On the other hand, serum aldosterone levels were two- to threefold higher in days 10-14 and 18-22 animals but fell to adult levels by day 25. In distal colon, amiloride-inhibitable electrogenic Na+ absorption was present at all ages but was significantly greater (P less than 0.01) in days 10-14 (3.8 +/- 0.5 mu eq.cm-2.h-1) and 18-22 (4.2 +/- 0.4) rabbits compared with adults (1.9 +/- 0.4) but not day 25-30 (2.8 +/- 0.5). In proximal colon, Na+ absorption was significantly higher (P less than 0.05) in day 10-14 (1.6 +/- 0.5 mu eq.cm-2.h-1) compared with day 18-22 (-0.2 +/- 0.5) and adults (0.06 +/- 0.5) and was amiloride insensitive. Neither chloride transport nor mucosal Na(+)-K(+)-ATPase demonstrated significant age-related changes in either region of colon. These results indicate that both proximal and distal colonic Na+ transport undergoes postnatal changes. In distal but not proximal colon these changes appear to be regulated by circulating aldosterone probably by increasing apical membrane permeability to Na+.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 349 ◽  
Author(s):  
Katalin Prokai-Tatrai ◽  
Daniel L. De La Cruz ◽  
Vien Nguyen ◽  
Benjamin P. Ross ◽  
Istvan Toth ◽  
...  

Using thyrotropin-releasing hormone (TRH) as a model, we explored whether synergistic combination of lipoamino acid(s) and a linker cleaved by prolyl oligopeptidase (POP) can be used as a promoiety for prodrug design for the preferential brain delivery of the peptide. A representative prodrug based on this design principle was synthesized, and its membrane affinity and in vitro metabolic stability, with or without the presence of a POP inhibitor, were studied. The in vivo formation of TRH from the prodrug construct was probed by utilizing the antidepressant effect of the peptide, as well as its ability to increase acetylcholine (ACh) synthesis and release. We found that the prototype prodrug showed excellent membrane affinity and greatly increased metabolic stability in mouse blood and brain homogenate compared to the parent peptide, yet a POP inhibitor completely prevented prodrug metabolism in brain homogenate. In vivo, administration of the prodrug triggered antidepressant-like effect, and microdialysis sampling showed greatly increased ACh release that was also antagonized upon a POP inhibitor treatment. Altogether, the obtained promising exploratory data warrant further investigations on the utility of the prodrug approach introduced here for brain-enhanced delivery of small peptides with neurotherapeutic potential.


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