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Toward Correction of the Genetic Defect in Cystic Fibrosis
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Larry G. Johnson, Richard C. Boucher
Current evidence suggests that CFTR is a cAMP-mediated Cl- channel (3336). However, CFTR also performs several regulatory functions including (1) regulation of the outwardly rectifying Cl- channel [ORCC (37,38)] and the alternative Cl- conductance Cla (39), the putative channel stimulated by calcium-mediated agonists, and (2) regulation of the epithelial Na+ channel [ENaC (40)]. Regulation of ENaC has special relevance since raised Na+ absorption, a feature of CF airway epithelia, leads to the raised airway transepithelial potential difference measured in CF patients (41-44). The expression of the ENaC subunits (α, β) in both serous and mucous gland cells suggest the possible presence of Na+ hyperabsorption in submucosal glands as well (45).
Neural Reflex Modulation of Intestinal Epithelial Transport
Published in T. S. Gaginella, Regulatory Mechanisms — in — Gastrointestinal Function, 2017
Cholera toxin-evoked secretion is the most thoroughly investigated, and a nervous involvement in this type of intestinal secretion is substantiated by two further observations made in vivo. First, the increase of transepithelial potential difference caused by the toxin was totally abolished by, e.g., hexamethonium.64Second, an increased release of VIP into the venous effluent was observed after exposing the intestinal mucosa to cholera toxin. After TTX was given, both fluid secretion and VIP release were markedly attenuated.65 Since VIP is contained only in nerves, the release of VIP suggests a participation of the ENS in cholera secretion.
Endothelins in the Lung
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Peter J. Henry, Roy G. Goldie, Douglas W. P. Hay
It is now clear that the airway epithelium is a major cellular source of ET-1 (9,23,24,31–33,40,43,254). Target cells for released ET-1 include adjacent airway smooth muscle cells, submucosal glands, nerves, inflammatory cells, and vascular smooth muscle cells. However, various epithelial cell functions can also be influenced by ET-1, suggesting that epithelial ET-1 might act as an autocrine, as well as a paracrine hormone within the airways (255–261). For example, ET-1 caused BQ-123-sensitive increases in [3H]thymidine incorporation and cell numbers in cultured porcine tracheal epithelial cells, indicating that ET-1, via ETA receptors, is mitogenic for epithelial cells (261). Furthermore, in epithelial cell cultures, ET-1 caused increases in the negativity of the transepithelial potential difference (258,260) and in the short-circuit current (255,257,260) caused by stimulation of Cl- transport across the epithelium (255,257,260). Dose-dependent increases in cilia beating frequency (257) and in the mucociliary activity in both nasal sinus and tracheal mucosae in the rabbit (259) have also been demonstrated in response to ET-1. The generation of cyclooxygenase products (255,257,259,260), including PGE2 (102,255,26), was responsible for directly mediating these effects. Of particular interest is the recent report that ET-1, via ETA receptors, depresses mucociliary clearance in ovine airways, independently of the involvement of prostanoids or peptidoleukotrienes (262). Epithelium-derived oxidative products of arachidonic acid metabolism released in response to ET-1 (256) are likely to modulate a range of physiological and patho-physiological processes within the lung (263).
Colonic paracellular permeability and circulating zonulin-related proteins
Published in Scandinavian Journal of Gastroenterology, 2021
Felipe Meira de-Faria, Olga Bednarska, Magnus Ström, Johan D. Söderholm, Susanna A. Walter, Åsa V. Keita
Colonic biopsies were mounted in Ussing chambers (Harvard apparatus Inc., Holliston, MA, USA) as previously described [29]. After equilibration for 40 min, the paracellular probe 51Chromium (Cr)-EDTA (Perkin Elmer, MA, USA) was added to the mucosal side of the tissues to a final concentration of 34 µCi/ml. Samples from the serosal sides of the chambers were collected at 0, 60 and 120 min and passage was measured in a gamma-reader (1282 Compugamma, Sweden). Further, 51Cr-EDTA permeability was calculated during the 60–120 min period and results are presented as Papp (apparent permeability coefficient; cm/s × 10−6). The transepithelial potential difference (PD) and the transepithelial resistance (TER) were monitored throughout the experiments to ensure tissue viability.