Endocytosis inhibitors abolish the active transport of polypeptides in the mucosa of the nasal upper concha of the rabbit

Cremaschi, D.; Porta, Cristina; Ghirardelli, Roberta; Manzoni, C.; Caremi, Italo

doi:10.1016/0005-2736(95)00263-4

Cited by 27 publications

(10 citation statements)

References 22 publications

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“…Previous studies have indicated the contribution of specific active transport processes in the absorption of peptides across nasal mucosa. Indeed, the transport of insulin, [1,7 Asu] eel-calcitonin, and ACTH have been proposed to occur through transepithelial receptor-mediated transcytosis processes across nasal epithelium (Cremaschi et al 1991(Cremaschi et al , 1996(Cremaschi et al , 1998(Cremaschi et al , 2001. Furthermore, a non-specific endocytosis has been shown for the permeation of human calcitonin across excised bovine nasal tissue .…”

Section: Discussionmentioning

confidence: 99%

“…The histology, viability, transepithelial electrical resistance (TEER) and aminopeptidase activity of the bovine nasal mucosa make it a suitable model to study the absorption of therapeutically relevant peptides (Schmidt et al , 2000. Previous studies have indicated that different regions of the nasal tissue may be involved in the active absorption of peptide drugs (Cremaschi et al 1991(Cremaschi et al , 1996. Also, by identifying regions with high permeability or specialized transport processes, it was hypothesized that drugs can be targeted and their systemic delivery enhanced (Chien & Chang 1987;Vidgren & Kublik 1998).…”

Section: Introductionmentioning

confidence: 99%

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Transport of deslorelin, an LHRH agonist, is vectorial and exhibits regional variation in excised bovine nasal tissue

Koushik

Kompella

2004

Journal of Pharmacy and Pharmacology

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The nasal route is a non-invasive alternative route for the delivery of a number of macromolecules, including peptides, proteins and vaccines. The purpose of this study was to determine the regional variation in excised bovine nasal tissue permeability to deslorelin, a nonapeptide luteinizing hormone releasing hormone (LHRH) agonist, and to further elucidate its mechanisms of transport. To this end, this study determined the permeability of deslorelin across different regions of freshly excised bovine nasal mucosa, including the medium turbinate anterior (MTA), medium turbinate posterior (MTP) and the inferior turbinate posterior (ITP) regions. At 37 degrees C, mucoal-to-serosal (m-s) transport of deslorelin across excised bovine nasal mucosa exhibited regional variation, with the % cumulative transport in 6 h being in the order: MTA (0.2 +/- 0.06%) < MTP (1.6 +/- 0.1%) < ITP (2.85 +/- 0.3%). In addition, at 37 degrees C, deslorelin transport across all these nasal regions was vectorial and the mucosal-to-serosal:serosal-to-mucosal (m-s:s-m) transport ratios across MTA, MTP and ITP regions were 1.5, 5.4 and 3.7, respectively. At low temperature (4 degrees C) and at 37 degrees C in the presence of 2,4-dinitrophenol, an energy depletor, the m-s deslorelin transport across the MTP region decreased to 0.32 +/- 0.12 and 0.13 +/- 0.05%, respectively, and the directionality was abolished. Sodium fluorescein transport also exhibited regional variation but no directionality. Histology and scanning electron microscopy studies indicated non-ciliated columnar epithelium in the MTA region and ciliated respiratory epithelium in the MTP and ITP regions. The thickness of the various regions, as visualized using histology, was in the order: MTA > MTP > ITP. Thus, deslorelin transport across excised bovine nasal mucosa is vectorial, temperature- and energy-dependent and exhibits regional variation. The regional differences in s-m transport are likely due to differences in the passive transport. Differences in m-s:s-m flux ratios may be due to differential expression of carriers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transport of deslorelin, an LHRH agonist, is vectorial and exhibits regional variation in excised bovine nasal tissue

Koushik

Kompella

2004

Journal of Pharmacy and Pharmacology

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“…PHZ, a specific inhibitor of the Na + /glucose cotransporter (SGLT 1),17,18 was added to the mucosal side. Cytochalasin B, an endocytosis inhibitor,19,20 was dissolved in ethanol due to its hydrophobicity. An aliquot of 25 μL of this ethanol solution was added to each side 5 min prior to the addition of Sit‐G NP, as it was reported that the addition of cytochalasin B to the basolateral side did not affect endocytosis 21 .…”

Section: Methodsmentioning

confidence: 99%

Regional Intestinal Absorption of FITC–Dextran 4,400 with Nanoparticles Based on β-Sitosterol β-D-Glucoside in Rats

Nakamura

Takayama

Nagai

et al. 2003

Journal of Pharmaceutical Sciences

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“…These observations suggest an uptake of the chimera into acidic endosomes, as GFP is quenched under acidic conditions. To test this, monensin (5 M) was used to block the pH differential in endosomes (24). There was no loss of P2X 1 -GFP fluorescence on exposure to ␣,␤ϪmeATP (10 M) in the presence of monensin (Figs.…”

Section: Properties Of the Currents Generated By Purinergic Agonists mentioning

confidence: 98%

The Distribution of P2X Receptor Clusters on Individual Neurons in Sympathetic Ganglia and Their Redistribution on Agonist Activation

Li¹,

Lee²,

Blair³

et al. 2000

Journal of Biological Chemistry

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The distribution of P2X receptors on neurons in rat superior cervical ganglia and lability of P2X receptors on exposure to agonists were determined. Antibody labeling of each P2X subtype P2X 1 -P2X 7 showed neurons isolated into culture possessed primarily P2X 2 subunits with others occurring in order P2X 7 > P2X 6 > P2X 3 > P2X 1 > P2X 5 > P2X 4 . Application of ATP and ␣,␤؊meATP to neurons showed they possessed a predominantly nondesensitizing P2X receptor type insensitive to ␣,␤؊ meATP, consistent with immunohistochemical observations. P2X 1 -green fluorescent protein (GFP) was used to study the time course of P2X 1 receptor clustering in plasma membranes of neurons and internalization of receptors following prolonged exposure to ATP. At 12-24 h after adenoviral infection, P2X 1 -GFP formed clusters about 1 m diameter in the neuron membrane. Application of ATP and ␣,␤؊meATP showed these neurons possessed a predominantly desensitizing P2X receptor type sensitive to ␣,␤؊meATP. Infection converted the major functional P2X receptor type in the membrane to P2X 1 . Exposure of infected neurons to ␣,␤؊meATP for less than 60 s led to the disappearance of P2X 1 -GFP fluorescence from the cell surface that was blocked by monensin, indicating the chimera is normally endocytosed into these organelles on exposure to agonist.P2X-type purinergic receptors consist of seven subtypes, classified as P2X 1 to P2X 7 , which form ligand-gated cation channels that contain cytoplasmic N and C termini and a large extracellular domain separating the two transmembrane segments (1). Antibodies against peptides from the C-terminal portion of the P2X 1 subtype have been used to determine the distribution of P2X 1 receptors in the vas deferens and urinary bladder, where they are found on the smooth muscle cells (2). Recently it has been shown that different P2X receptor subtypes form clusters of two different sizes on the smooth muscle cells of the rat urinary bladder, vas deferens, and blood vessels: large numbers of small clusters of about 0.4-m diameter distributed over the smooth muscle and small numbers of large clusters greater than 1-m diameter positioned under junctional varicosities (3-5). The large junctional P2X clusters can be observed during normal development to be formed from small clusters of a number of different subtypes, which gather in large numbers in the vicinity of the nerve varicosities (6). Sympathetic ganglion cells were reported to possess P2X receptors, primarily of the P2X 2 , P2X 4 , and P2X 6 subtypes (7), and transcripts for P2X 1 , P2X 2 , P2X 4 , and P2X 6 are present (8), although it is not known whether these receptors are organized into large and small clusters and if so whether the large clusters are found beneath boutons as expected if they mediate some aspect of transmission. In the present work, both large and small clusters of different P2X subunit types are shown to exist on ganglion cells, and their spatial disposition with respect to preganglionic boutons has been ascertained.The existence of P2...

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Endocytosis inhibitors abolish the active transport of polypeptides in the mucosa of the nasal upper concha of the rabbit

Cited by 27 publications

References 22 publications

Transport of deslorelin, an LHRH agonist, is vectorial and exhibits regional variation in excised bovine nasal tissue

Transport of deslorelin, an LHRH agonist, is vectorial and exhibits regional variation in excised bovine nasal tissue

Regional Intestinal Absorption of FITC–Dextran 4,400 with Nanoparticles Based on β-Sitosterol β-D-Glucoside in Rats

The Distribution of P2X Receptor Clusters on Individual Neurons in Sympathetic Ganglia and Their Redistribution on Agonist Activation

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