PERMEATION AND PATHWAYS OF HUMAN CALCITONIN (HCT) ACROSS EXCISED BOVINE NASAL-MUCOSA

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 confo cal laser scanning microscopy. Permeabilities of gonadorelin, busereli n, Hoe0l3, and of thymopoietin fragments TP5 and TP4 were also include d. Apparent permeability coefficients (P-eff) ranged between 4 x 10(-5 ) (SMS) and 1.7 x 10(-5) cm s(-1) (TP4). Such P-eff are typical for le aky-type airway epithelia. The order of permeabilities was: SMS much g reater than hCT, sCT > buserelin, Hoe013 much greater than TP5 > TP4, LHRH. The relatively high permeability of hCT and sCT contrasted to th eir high molecular weight. At 37 degrees C, the permeability of hCT fr om mucosal to serosal (m-to-s) was found two-fold higher (p < 0.05) th an from serosal to mucosal (s-to-m). Controls using H-3-mannitol showe d 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). A s evaluated by confocal laser scanning microscopy, uptake studies with FITC-18-hCT revealed intracellular fluorescence in the epithelial cel ls, at 10 min/10 mu M 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. (C) 1998 Elsevier Science Inc.