The microcirculation and solute exchange
Neil Herring, David J. Paterson in Levick's Introduction to Cardiovascular Physiology, 2018
In stark contrast to most capillaries, cerebral capillaries rely on specific carrier proteins in the endothelial cell membrane to transport essential, lipid-insoluble solutes between the blood and brain parenchyma. There are specific carrier proteins for D-glucose, the natural, dextrose form of glucose (carrier glucose transporter 1, GLUT-1), lactate, pyruvate, amino acids and adenosine. This form of transport is transcellular, as opposed to paracellular. The transport is not active, but is brought about by the diffusion of the carrier-bound solute down its concentration gradient (facilitated diffusion). In addition, the cerebral endothelium can regulate the K+ concentration of cerebral interstitial fluid by active transport, via Na+/K+-ATPase in the ablumi- nal membrane (Section 15.4).
Immune function of epithelial cells
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Many luminal materials, including hydrophilic nutrients, are transported by distinct transport proteins within apical and basolateral domains. Most often, apical transporters take advantage of the steep, electrochemical Na+ gradient (from extracellular to intracellular) to provide the driving force for absorption. The basolateral Na+-K+ATPase that maintains the Na+ gradient and pumps apically transported Na+ ions across the basolateral membrane is, therefore, essential to ongoing nutrient transport. Paracellular recycling of Na+ ions from the lamina propria to the lumen (via the tight junction, as discussed later) is essential, as the diet does not otherwise contain sufficient Na+ to support ongoing apical absorption. Solutes absorbed by apical transmembrane transport proteins cross the basolateral membrane via facilitated transporters that operate in a strictly concentration-dependent manner. This allows the basolateral transport proteins to drive nutrient absorption from the enterocyte cytoplasm toward the bloodstream when nutrients are being actively absorbed but to also operate in the reverse direction in order to bring nutrients into the enterocyte when none are present in the lumen, e.g., during fasting. Whether by vesicles or transmembrane transport proteins, transport of solutes, membranes, and cargo from one side, through the cell to the other side, is termed the “transcellular pathway” and is an energy-dependent process.
Evaluation Models for Drug Transport Across the Blood–Brain Barrier
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
Parallel artificial membrane permeability assay (PAMPA) model was proposed for studying CNS permeability. Porcine brain lipid extract dissolved in n-dodecane serves as PAMPA membrane barrier. The permeability characteristics of chemical compounds can be determined by a combined solubility permeability assay method (Wexler et al., 2005). In this method, it involves the determination of solubility at different pH values. The filtered saturated solution acts as an input material for BBB permeability. This method offers certain merits like reduced of sample usage and preparation time, removal of interference, maximization of input concentration and optimization of the sample to track. A combined approach of both active and passive transporter studies helps in differentiation between paracellular and transcellular components of transport (Kerns et al., 2004).
Anti-ageing peptides and proteins for topical applications: a review
Published in Pharmaceutical Development and Technology, 2022
Mengyang Liu, Shuo Chen, Zhiwen Zhang, Hongyu Li, Guiju Sun, Naibo Yin, Jingyuan Wen
The transcellular pathway refers to the transportation of solutes through a cell, including transcellular passive diffusion, transcellular active transport, and transcytosis (Kasting et al. 2019). Diffusion is the movement of chemicals from a region of higher concentration to a region of lower concentration. Active transport, also known as carrier-mediated transport, involves using energy to help specific molecules move across the barrier and against the concentration gradient (Fung et al. 2018). Since the cell membrane is lipophilic, it might resist the passive diffusion of hydrophilic or charged compounds. Transcytosis is another type of transcellular route, where macromolecules are carried across the cell membranes (Liu et al. 2019). These macromolecules are captured in vesicles on the side of the cell, drawn across the cell, and then ejected on the other side (Liu et al. 2019). However, most experimental studies suggest that the primary pathway across SC is the intercellular pathway, as described below.
Low colonic absorption drugs: risks and opportunities in the development of oral extended release products
Published in Expert Opinion on Drug Delivery, 2018
Jin Xu, Yiqing Lin, Pierre Boulas, Matthew L. Peterson
The transcellular route refers to passage of a molecule through the lipophilic membrane. Therefore, transport through the transcellular route is favored for unionized lipophilic compounds. The majority of drugs are ionizable and the ionization state of drugs at different physiological pH can impact the absorption. For example, aspirin, with pKa of 3.5, is readily absorbed in its unionized form at acidic condition, but more slowly in its ionized form when the gastric pH is close to neutral. Moreover, the average pH of human small intestine and large intestine are usually in the range of 6–7.5 and high values of pH up to 9 have occasionally been found [23]. The pH variance along the GI track can alter the ionization state of a compound with pKa within this range and further impact the solubility and the absorption of the compound at different GI regions. For instance, the LCA drug Carvedilol has a pKa of 7.8 [24] and aqueous solubility at pH 5, 7, and 9 are 100, 23, and <1 μg/ml, respectively [25]. Carvedilol absorption in the lower GI tract is believed to be limited by its pH-dependent solubility rather than the permeability [26].
Overview of intranasally delivered peptides: key considerations for pharmaceutical development
Published in Expert Opinion on Drug Delivery, 2018
Wisam Al Bakri, Maureen D. Donovan, Maria Cueto, Yunhui Wu, Chinedu Orekie, Zhen Yang
Along with MW, the size and shape of peptide molecules also affect the uptake of peptides across the nasal mucosa. McMartin et al. reported that cyclic molecules with smaller molecular radii have an improved absorption compared with linear molecules. The same investigators suggested that the transport of polar molecules could occur in three possible ways: 1) transcytosis, which involves uptake into vesicles formed along the cell membrane; 2) transcellular transport, which includes passive partitioning and carrier-mediated transport across the cell membrane; and 3) paracellular transport through the tight junctions [13,42]. Endocytotic vesicles range in size from about 60 nm (600 Å) to a few microns [43,44], and therefore can participate in the uptake of large molecules such as peptides. Richard et al. reported that wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) (MW 38,000 Da) delivered intranasally is endocytosed by the olfactory neurons [45]. Balin et al. observed that WGA-HRP administered intranasally passes freely through the paracellular spaces within 45–90 min [46]. McMartin suggested that paracellular transport through the tight junctions is one of the most important uptake pathways through which peptides are absorbed across the nasal epithelium [13].
Related Knowledge Centers
- Calcium
- Electrochemical Gradient
- Glucose
- Molecule
- Potassium
- Sodium
- Active Transport
- Solution
- Cell
- Adenosine Triphosphate