Gastrointestinal Tract as a Major Route of Pharmaceutical Administration
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
A symporter is an integral membrane protein that is involved in the transport of many differing types of molecules across the cell membrane. The symporter works in the plasma membrane and molecules are transported across the cell membrane at the same time, and is, therefore, a type of cotransporter. The transporter is called a symporter, because the molecules will travel in the same direction in relation to each other. In this type of indirect active transport, the driving ion (usually Na+) is forced through the membrane pump in the same direction as a second molecule or ion. An example of this is the Na+/glucose transporter in which the transmembrane protein permits Na+ ions and glucose to enter the cell together. The Na+ ions flow down their concentration gradient while the glucose molecules are pumped against their concentration gradient. Eventually, the Na+ is pumped back out of the cell by the Na+/K+ ATPase. This pump is used to actively transport glucose out of the GI tract and into the circulatory system (Youn et al., 2009).
Thyroid radionuclide imaging and therapy in thyroid cancer
Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner in Endocrine Surgery, 2017
Patients with poorly differentiated carcinoma and in the older age group tend to have poor uptake of I-131, which is associated with poor prognosis. Even patients with initially good tumor uptake of RAI develop loss of RAI uptake in metastatic disease over time, leading to poorer response to RAI therapy and worse prognosis. In these cases, there appears to be loss of the human iodide symporter (hNIS). Research efforts have attempted to restore the iodide symporter through the use of hNIS gene transfer into hNIS-defective tumors. Challenges with this approach include delivery of the gene, usually requiring direct local injection, and only transient efficacy for the carrier adenovirus. Moreover, increased uptake of RAI by the restored symporter does not necessarily lead to prolonged retention, if there is also poor organification capability. With this approach, Smit et al. [39] found higher high peak iodide accumulation, and the half-life was increased in hNIS-deficient mice. A lethal dose of radioiodine could not be delivered, however, although tumor development was delayed in thyroid-ablated, low-iodide-diet mice treated with radioiodine therapy. This has been tried as well in cancers other than thyroid cancer. Park et al. [40] investigated in mice the feasibility of combination gene therapy and noninvasive radionuclide imaging after expression of human hNIS and inhibition of multidrug resistance (MDR1) with the aid of a cytomegalovirus promoter, in order to effect enhanced response to both I-131 and doxorubicin, with encouraging results.
Imaging of the thyroid gland
Pallavi Iyer, Herbert Chen in Thyroid and Parathyroid Disorders in Children, 2020
Technetium scan (Tc99m) pertechnetate (99mTcO4–) is a radio-isotope that mimics iodine and is used for thyroid imaging. It is administered via intravenous injection and is trapped in the thyrocyte via the sodium iodide symporter in the thyroid cell. The thyroid gland is scanned 20 minutes after administration to reveal the location and size of the thyroid gland compared to the locations of the markers (Figure 2.2). This study is helpful in distinguishing between the causes of congenital hypothyroidism (sublingual thyroid gland, lingual thyroid gland, thyroid aplasia, and eutopic thyroid gland). Maternal blocking antibodies may sometimes interfere with the study and note an aplastic thyroid gland, but an ultrasound reveals a eutopic thyroid gland. This study is best performed when the TSH is elevated and thus upregulating the sodium-iodide symporter (NIS) expression (1,2).
Efflux pump inhibitors as a promising adjunct therapy against drug resistant tuberculosis: a new strategy to revisit mycobacterial targets and repurpose old drugs
Published in Expert Review of Anti-infective Therapy, 2020
Liliana Rodrigues, Pedro Cravo, Miguel Viveiros
This strategy also identified several antiarrhythmic, antihypertensive drugs that potentially target a probable metal cation transporter P-type ATPase A CtpF (Rv1997) in M. tuberculosis. Deslanoside is a cardiac glycoside used to treat congestive heart failure, supraventricular arrhythmias and to control ventricular rate in the treatment of chronic atrial fibrillation. This compound inhibits the Na+/K+-ATPase pump, resulting in an increase in intracellular sodium and calcium concentrations that may promote activation of contractile proteins, such as actin and myosin [162]. Acetyldigitoxin is a cardioactive derivative of lanatoside A or of digitoxin used for fast digitalization in congestive heart failure. The proposed mode of action is similar to deslanoside: inhibition of the Na+/K+ pump that leads to increased amounts of calcium [163]. Ethacrynic acid is used in the treatment of high blood pressure and edema caused by diseases like congestive heart failure, liver failure, and kidney failure. It inhibits the symport of sodium, potassium, and chloride primarily in the ascending limb of Henle. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid [164]. Finally, the last drug in this group is bretylium, used in emergency medicine, cardiology, and other specialties for the acute management of ventricular tachycardia and ventricular fibrillation. The main mode of action for bretylium is thought to be inhibition of voltage-gated potassium channels and the Na+/K+-ATPase [165].
Auto regulatory capacity of the thyroid gland after numerous iodinated contrast media investigations
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2020
Thomas Bøhmer, Zivar Bachtyari, Christine Sommer, Sara Salehi Hammerstad
Iodine is necessary for thyroid hormone synthesis. The recommended dietary allowance of iodine is 150 ug/d (WHO recommendation), whereas about half is used in the thyroid gland. Excessive intake of iodine inhibits the organic binding of iodide in the normal thyroid, named ‘Wolf-Chaikoff effect’ [1]. The thyroid escapes this inhibition in most people after a few weeks due to decrease in expression of sodium-iodide-symporter [2].
Incidence and risk factors for radioactive iodine-induced sialadenitis
Published in Acta Oto-Laryngologica, 2020
Alvaro Sánchez Barrueco, Fernando González Galán, Ignacio Alcalá Rueda, Jessica Mireya Santillán Coello, María Pilar Barrio Dorado, José Miguel Villacampa Aubá, Manuel Escanciano Escanciano, Lucía Llanos Jiménez, Ignacio Mahillo Fernández, Carlos Cenjor Español
The Na+/I− symporter (NIS) plays a major role in the side effects of therapy with radioactive iodine [3]. The radiation from radioiodine damages this plasma trasmembrane glycoprotein which is highly expressed throughout the thyroid tissue but also in the basolateral membranes of the striated ducts, yet it is weakly expressed in few intercalated and excretory duct cells within the salivary glands.
Related Knowledge Centers
- Antiporter
- Cotransporter
- Facilitated Diffusion
- Glucose
- Integral Membrane Protein
- Cell Membrane
- Active Transport
- Membrane Transport Protein
- Sodium-Glucose Transport Proteins
- Oral Rehydration Therapy