title: Permeation and pathways of human calcitonin (hCT) across excised bovine nasal mucosa.
abstract: In vitro permeation of human calcitonin (hCT), salmon calcitonin (sCT), and the somatostatin analog octreotide (SMS) through excised bovine nasal mucosa was studied applying donor/receiver experiments and confocal laser scanning microscopy. Permeabilities of gonadorelin, buserelin, Hoe013, and of thymopoietin fragments TP5 and TP4 were also included. Apparent permeability coefficients (Peff) ranged between 4 x 10(-5) (SMS) and 1.7 x 10(-5) cm s(-1) (TP4). Such Peff are typical for leaky-type airway epithelia. The order of permeabilities was: SMS >> hCT, sCT > buserelin, Hoe013 >> TP5 > TP4, LHRH. The relatively high permeability of hCT and sCT contrasted to their high molecular weight. At 37 degrees C, the permeability of hCT from mucosal to serosal (m-to-s) was found two-fold higher (p < 0.05) than from serosal to mucosal (s-to-m). Controls using 3H-mannitol showed equal permeabilities in both directions. At 4 degrees C, permeation of hCT was reduced but equal in both directions (m-to-s and s-to-m). As evaluated by confocal laser scanning microscopy, uptake studies with FITC-18-hCT revealed intracellular fluorescence in the epithelial cells, at 10 min/10 microM exposure in the form of fluorescent vesicles. By combination of these findings, an endocytotic pathway is suggested to contribute to the transport of hCT through nasal epithelium.
authors.affiliation: Department of Pharmacy, Swiss Federal Institute of Technology Zurich (ETH), Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: B
authors.initials: B
authors.lastname: Rothen-Rutishauser
authors.forename: J C
authors.initials: JC
authors.lastname: Perriard
authors.forename: M C
authors.initials: MC
authors.lastname: Schmidt
authors.forename: H P
authors.initials: HP
authors.lastname: Merkle
mesh_terms: D000818:Animals; D001692:Biological Transport; D002116:Calcitonin / Q000378:metabolism*; D002417:Cattle; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008856:Microscopy, Fluorescence; D009297:Nasal Mucosa / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010539:Permeability; D013696:Temperature
chemical_list: D005456:Fluorescent Dyes; D010455:Peptides; D002116:Calcitonin