Intestinal drug transporters in pathological states: an overview

Abstract Emerging information suggests that gastrointestinal and systemic pathology states may affect expression and function of membrane transporters in the gastrointestinal tract. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that in some pathologies, e.g., liver or kidney failure, changes in the intestinal transporter function provide compensatory functions, eliminating substrates excreted by dysfunctional organs. A literature search was conducted on Ovid and Pubmed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of intestinal drug transporters. The accumulated data suggest that gastrointestinal pathology (inflammatory bowel disease, celiac disease, cholestasis) as well as systemic pathologies (kidney failure, liver failure, hyperthyroidism, hyperparathyroidism, obesity, diabetes mellitus, systemic inflammation and Alzheimer disease) may affect drug transporter expression and function in the gastrointestinal tract. The altered status of drug transporters may provide compensatory activity in handling endogenous compounds, affect local drug actions in the gastrointestinal tract as well as impact drug bioavailability. Graphic abstract

Download Full-text

Extrahepatic Drug Transporters in Liver Failure: Focus on Kidney and Gastrointestinal Tract

International Journal of Molecular Sciences ◽

10.3390/ijms21165737 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5737 ◽

Cited By ~ 1

Author(s):

Marek Droździk ◽

Stefan Oswald ◽

Agnieszka Droździk

Keyword(s):

Gastrointestinal Tract ◽

Liver Failure ◽

Liver Dysfunction ◽

Drug Transporters ◽

Endogenous Compounds ◽

Clinical Consequences ◽

Drug Actions ◽

And Function ◽

Drug Pharmacokinetics

Emerging information suggests that liver pathological states may affect the expression and function of membrane transporters in the gastrointestinal tract and the kidney. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that changes in intestinal and kidney transporter functions provide the compensatory activity of eliminating endogenous compounds (e.g., bile acids) generated and accumulated due to liver dysfunction. A literature search was conducted on the Ovid and PubMed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of the gastrointestinal and kidney operating ABC (ATP-binding cassette) transporters and SLC (solute carriers) carriers. The accumulated data suggest that liver failure-associated transporter alterations in the gastrointestinal tract and kidney may affect drug pharmacokinetics. The altered status of drug transporters in those organs in liver dysfunction conditions may provide compensatory activity in handling endogenous compounds, affecting local drug actions as well as drug pharmacokinetics.

Download Full-text

The Gastrointestinal Tract of the White-Throated Woodrat (Neotoma albigula) Harbors Distinct Consortia of Oxalate-Degrading Bacteria

Applied and Environmental Microbiology ◽

10.1128/aem.03742-13 ◽

2013 ◽

Vol 80 (5) ◽

pp. 1595-1601 ◽

Cited By ~ 45

Author(s):

Aaron W. Miller ◽

Kevin D. Kohl ◽

M. Denise Dearing

Keyword(s):

Gastrointestinal Tract ◽

High Throughput Sequencing ◽

Gut Contents ◽

Content Type ◽

Degrading Bacteria ◽

Plant Secondary Compound ◽

And Function ◽

Toxic Plant ◽

Dietary Oxalate

ABSTRACTThe microbiota inhabiting the mammalian gut is a functional organ that provides a number of services for the host. One factor that may regulate the composition and function of gut microbial communities is dietary toxins. Oxalate is a toxic plant secondary compound (PSC) produced in all major taxa of vascular plants and is consumed by a variety of animals. The mammalian herbivoreNeotoma albigulais capable of consuming and degrading large quantities of dietary oxalate. We isolated and characterized oxalate-degrading bacteria from the gut contents of wild-caught animals and used high-throughput sequencing to determine the distribution of potential oxalate-degrading taxa along the gastrointestinal tract. Isolates spanned three genera:Lactobacillus,Clostridium, andEnterococcus. Over half of the isolates exhibited significant oxalate degradationin vitro, and allLactobacillusisolates contained theoxcgene, one of the genes responsible for oxalate degradation. Although diverse potential oxalate-degrading genera were distributed throughout the gastrointestinal tract, they were most concentrated in the foregut, where dietary oxalate first enters the gastrointestinal tract. We hypothesize that unique environmental conditions present in each gut region provide diverse niches that select for particular functional taxa and communities.

Download Full-text

Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2013.01.004 ◽

2013 ◽

Vol 41 (5) ◽

pp. 484-487 ◽

Cited By ~ 31

Author(s):

Johanna Weiss ◽

Walter Emil Haefeli

Keyword(s):

Drug Transporters ◽

The Novel ◽

Antiretroviral Drug ◽

And Function ◽

Drug Metabolising Enzymes

Download Full-text

Membrane Carriers and Transporters in Kidney Physiology and Disease

Biomedicines ◽

10.3390/biomedicines9040426 ◽

2021 ◽

Vol 9 (4) ◽

pp. 426

Author(s):

Marek Drozdzik ◽

Maria Drozdzik ◽

Stefan Oswald

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Drug Interactions ◽

Kidney Physiology ◽

Affect Expression ◽

Clinical Consequences ◽

Drug Actions ◽

Membrane Carriers ◽

And Function ◽

Drug Pharmacokinetics

The growing information suggests that chronic kidney disease may affect expression and function of membrane carriers and transporters in the kidney. The dysfunction of carriers and transporters entails deficient elimination of uremic solutes as well as xenobiotics (drugs and toxins) with subsequent clinical consequences. The renal carriers and transporters are also targets of drugs used in clinical practice, and intentional drug–drug interactions in the kidney are produced to increase therapeutic efficacy. The understanding of membrane carriers and transporters function in chronic kidney disease is important not only to better characterize drug pharmacokinetics, drug actions in the kidney, or drug–drug interactions but also to define the organ pathophysiology.

Download Full-text

Potential of novel antiretrovirals to modulate expression and function of drug transporters in vitro

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkq501 ◽

2011 ◽

Vol 66 (4) ◽

pp. 802-812 ◽

Cited By ~ 48

Author(s):

N. C. L. Zembruski ◽

G. Buchel ◽

L. Jodicke ◽

M. Herzog ◽

W. E. Haefeli ◽

...

Keyword(s):

Drug Transporters ◽

And Function

Download Full-text

Molecular architecture and functions of the neuronal cytoskeleton

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100157541 ◽

1990 ◽

Vol 48 (3) ◽

pp. 2-3

Author(s):

Nobutaka Hirokawa

Keyword(s):

Major Elements ◽

Molecular Structures ◽

Organelle Transport ◽

Molecular Architecture ◽

Neuronal Morphogenesis ◽

Microtubule Associated Proteins ◽

Associated Proteins ◽

And Function ◽

Small Clusters

In this symposium I will present our studies about the molecular architecture and function of the cytomatrix of the nerve cells. The nerve cell is a highly polarized cell composed of highly branched dendrites, cell body, and a single long axon along the direction of the impulse propagation. Each part of the neuron takes characteristic shapes for which the cytoskeleton provides the framework. The neuronal cytoskeletons play important roles on neuronal morphogenesis, organelle transport and the synaptic transmission. In the axon neurofilaments (NF) form dense arrays, while microtubules (MT) are arranged as small clusters among the NFs. On the other hand, MTs are distributed uniformly, whereas NFs tend to run solitarily or form small fascicles in the dendrites Quick freeze deep etch electron microscopy revealed various kinds of strands among MTs, NFs and membranous organelles (MO). These structures form major elements of the cytomatrix in the neuron. To investigate molecular nature and function of these filaments first we studied molecular structures of microtubule associated proteins (MAP1A, MAP1B, MAP2, MAP2C and tau), and microtubules reconstituted from MAPs and tubulin in vitro. These MAPs were all fibrous molecules with different length and formed arm like projections from the microtubule surface.

Download Full-text

Decision letter for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v2/decision1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

Download Full-text

Review for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v1/review1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

Download Full-text

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614605 ◽

1999 ◽

Vol 81 (06) ◽

pp. 951-956 ◽

Cited By ~ 59

Author(s):

J. Corral ◽

R. González-Conejero ◽

J. Rivera ◽

F. Ortuño ◽

P. Aparicio ◽

...

Keyword(s):

Venous Thrombosis ◽

Cell Types ◽

Receptor Expression ◽

Case Control Studies ◽

Platelet Surface ◽

Vitro Analysis ◽

And Function ◽

In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

Download Full-text