Nasal epithelium active transport

Drug absorption occurs from the site(s) of drug absorption (e.g., gut, lung, nasal epithelium) by either active (e.g., transport mediated) or passive mechanisms. The bioavailability (F) of a drug is the fraction that reaches the systemic circulation and is ultimately avail-... 

The nasal epithelium possesses selective absorption characteristics similar to those of a semipermeable membrane, i.e., it allows a rapid passage of some compounds while preventing the passage of others. The process of transportation across the nasal mucosa involves either passive diffusion, via paracellular or transcellular mechanisms, or occurs via active processes mediated by membrane-bound carriers or membrane-derived vesicles involving endo- or transcytosis. 

Active transport mechanisms for di- and tri-peptides, as well as L-amino acids, have been demonstrated in the nasal epithelium. 

Figure 6. Amino acid-induced activity patterns were examined in more detail using the calcium-sensitive dye CalciumGreen (Friedrich and Korsching 1997). Like ANEPPQ, this dye was introduced by anterograde transport from the nasal epithelium and thus labeled only the axons and terminals of the olfactory receptor cell axons. In contrast to the voltage-sensitive dye, signals originate only in terminal presynap-tic regions, and are therefore more focal in nature than those of the voltage-dependent dye, which originate from both axons and terminals.

The thin, porous and highly vascularised nasal epithelium has a high total blood flow, which facilitates fast absorption of substances. Direct transport to the systemic circulation or the central nervous system makes it possible to obtain a rapid therapeutic effect. The intranasal absorption depends on the mucociliary clearance, pathological conditions such as infections, allergy and obstruction, mucus secretion, moisture content, enzymatic degradation, and blood flow. It should be remembered that the blood flow can be affected by either locally or systemically active substances. These phenomena can determine the nasal absorption of substances. Oxymetazoline and clonidine reduce the blood flow, while phenylephrine and salbutamol raise it. 

The surface of the nasal cavity is approximately 150 cm. Inside the cavity, the mucosa is covered with the ciliary epithelium. The ciliary activity is the driving force of the secretory transport in the nose. Approximately 1 L of mucus is transported from the anterior part to the posterior part of the nose per day. The mucus in the rear of the cavity is removed by swallowing. The function of the ciliary activity is to remove any particles that are trapped on the mucus blanket during inhalation. It takes approximately 20-30 min for the whole mucus layer to be renewed. 

The discriminatory capacity of the mammalian olfactory system is such that thousands of volatile chemicals are perceived as having distinct odors. It is accepted that the sensation of odor is triggered by highly complex mixtures of volatile molecules, mostly hydrophobic, and usually occurring in trace-level concentrations (ppm or ppb). These volatiles interact with odorant receptors of the olfactive epithelium located in the nasal cavity. Once the receptor is activated, a cascade of events is triggered to transform the chemical-structural information contained in the odorous stimulus into a membrane potential [58,59], which is projected to the olfactory bulb and then transported to higher regions of the brain [60] where the translation occurs. 

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