Plasma membrane diffusion through

The two most common temporal input profiles for dmg delivery are zero order (constant release), and half order, ie, release that decreases with the square root of time. These two profiles correspond to diffusion through a membrane and desorption from a matrix, respectively (1,2). In practice, membrane systems have a period of constant release, ie, steady-state permeation, preceded by a period of either an increasing (time lag) or decreasing (burst) flux. This initial period may affect the time of appearance of a dmg in plasma on the first dose, but may become insignificant upon multiple dosing. 

Ethylene is slightly more potent as an anesthetic than nitrous oxide, and the smell of ethylene causes choking. Diffusion through the alveolar membrane is sufficiendy rapid for equilibrium to be estabUshed between the alveolar and the pulmonary capillary blood with a single exposure. Ethylene is held both ia cells and ia plasma ia simple physical solution. The Hpoid stroma of the red blood cells absorb ethylene, but it does not combine with hemoglobin. The concentration ia the blood is 1.4 mg/mL when ethylene is used by itself for anesthesia. However, ia the 1990s it is not used as an anesthetic agent. 

The passage of a small and/or highly lipophilic molecule through the membrane phospholipid bilayer according to the gradient of its concentrations across the plasma membrane. It is slower than facilitated diffusion, which, however, also follows the gradient of solute concentrations across the membrane. 

For all commonly used routes of administration except intravenous, the drug must dissolve in body fluids and diffuse through one or more membranes to enter the plasma. Thus, all routes except intravenous are classed as extravascular routes, and absorption is defined as appearance of the drug in plasma. 

Figure 1 General pathways through which molecules can actively or passively cross a monolayer of cells. (A) Endocytosis of solutes and fusion of the membrane vesicle with the opposite plasma membrane in an active process called transcytosis. (B) Similar to A, but the solute associates with the membrane via specific (e.g., receptor) or nonspecific (e.g., charge) interactions. (C) Passive diffusion between the cells through the paracellular space. (C, C") Passive diffusion (C ) through the cell membranes and cytoplasm or (C") via partitioning into and lateral diffusion within the cell membrane. (D) Active or carrier-mediated transport of an otherwise poorly membrane permeable solute into and/or out of a cellular barrier.

Most hydrophilic, or water-soluble, substances are repelled by this hydrophobic interior and cannot simply diffuse through the membrane. Instead, these substances must cross the membrane using specialized transport mechanisms. Examples of lipid-insoluble substances that require such mechanisms include nutrient molecules, such as glucose and amino acids, and all species of ions (Na+, Ca++, H+, Cl, and HC03). Therefore, the plasma membrane plays a very important role in determining the composition of the intracellular fluid by selectively permitting substances to move in and out of the cell. 

Formation of Na+, K+-ATPase carrier molecules in the basolateral membrane of the tubular epithelial cells (promotes extrusion of Na+ ions from the cells and their movement into plasma by way of peritubular capillaries enhances the concentration gradient for passive diffusion through Na+ channels in the luminal membrane)... 

The oft-touted argument against a physiological role for HbSNO is that even if it does form in RBCs, the Hb-bound NO has to make quite a journey to get to smooth muscle cells it must first cross the RBC plasma membrane, then the RBC free zone (Liao et al., 1999), then cross the endothelial cell membranes twice and finally go through the smooth muscle membrane. Why would nature adopt such a convoluted route when the endothelial cells next to the smooth muscle cells are producing membrane-diffusable NO ... 

The intestinal absorption of dietary cholesterol esters occurs only after hydrolysis by sterol esterase steryl-ester acylhydrolase (cholesterol esterase, EC 3.1.1.13) in the presence of taurocholate [113][114], This enzyme is synthesized and secreted by the pancreas. The free cholesterol so produced then diffuses through the lumen to the plasma membrane of the intestinal epithelial cells, where it is re-esterified. The resulting cholesterol esters are then transported into the intestinal lymph [115]. The mechanism of cholesterol reesterification remained unclear until it was shown that cholesterol esterase EC 3.1.1.13 has both bile-salt-independent and bile-salt-dependent cholesterol ester synthetic activities, and that it may catalyze the net synthesis of cholesterol esters under physiological conditions [116-118], It seems that cholesterol esterase can switch between hydrolytic and synthetic activities, controlled by the bile salt and/or proton concentration in the enzyme s microenvironment. Cholesterol esterase is also found in other tissues, e.g., in the liver and testis [119][120], The enzyme is able to catalyze the hydrolysis of acylglycerols and phospholipids at the micellar interface, but also to act as a cholesterol transfer protein in phospholipid vesicles independently of esterase activity [121],... 

Water enters cells not only via channels but also by diffusion through the plasma membrane, although the quantities of water in the latter case are likely to be small. It also enters via endocytosis (see below). 

Although fatty acids are lipid soluble and might be expected to diffuse through the plasma membrane sufficiently rapidly to satisfy the required rates of oxidation, this is not the case and a transporter protein is present in the plasma membrane. 

Muscle contraction is triggered by motor neurons that release the neurotransmitter acetylcholine (see p. 352). The transmitter diffuses through the narrow synaptic cleft and binds to nicotinic acetylcholine receptors on the plasma membrane of the muscle cell (the sarcolemma), thereby opening the ion channels integrated into the receptors (see p. 222). This leads to an inflow of Na which triggers an action potential (see p. 350) in the sarcolemma. The action potential propagates from the end plate in all directions and constantly stimulates the muscle fiber. With a delay of a few milliseconds, the contractile mechanism responds to this by contracting the muscle fiber. 

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