Cholinergic hypersecretion may be identified by relief of rhinorrhea when sitagliptin sensitive subjects use an anticholinergic nasal spray. Analysis of the nasal secretions may distinguish glandular FTY720 manufacturer from vascular sources of the discharge, and the nature of the offending peptide. These putative peptide DPP IV substrates may be targets for development of novel rhinorrhea, antitus sive, and bronchodilator drugs. Sitagliptin joins the list of drugs associated with nonallergic mechanisms of rhinitis. DPP IV immunoreactive material has been localized to human nasal and bronchial mucosa. Immunore active material was present in apical cells of submucosal glands, leukocytes, and endothelial cells. Biopsies of human nasal tissue from chronic rhinos inusitis and bronchi in chronic obstructive diseases dem onstrated Inhibitors,Modulators,Libraries a positive correlation between DPP IV enzyme activity and immunoreactivity.

DPP IV enzyme activities in human airway biopsies were inversely related to mucosal inflammatory cell density. The leukocytes were Inhibitors,Modulators,Libraries predominantly memory T cells and monocytes. The inverse relationship suggested that products of the inflammatory process Inhibitors,Modulators,Libraries inhibited Inhibitors,Modulators,Libraries DPP IV expression. DPP IV is also known as CD26, and is highly expressed on memory T cells. CD26 plays an important role in the proliferation of memory T cells in response to antigen presentation. Activation of CD26 may increase CD86 expression on CD14 positive monocytes and other anti gen presenting cells. DPP IV degrades interferon gamma induced chemokines, CCL3, CCL5, CCL11, CCL22, and CXCL12.

This effect may bias mucosal immune responses towards TH2 compared to TH1 lymphocyte phenotype. DPP IV cleavage of the N terminal dipeptide from CCL5 enhanced chemotaxis of T cells, but not monocytes, in vitro. A soluble Inhibitors,Modulators,Libraries form of DPP IV is elevated in asthma. Plasma sCD26 was positively correlated with aberrant expression of cell surface CD26 on a wide range of lymphocytes, altered peripheral eosinophils, Th2 related chemokines CCL5 and CCL22, and the costimula tory molecule soluble cytotoxic T lymphocyte antigen 4. These cellular mechanisms may augment the consequences of DPP IV inhibitors dur ing tissue inflammation. Increased attachment of sialic acid residues to the N linked polysaccharides of DPP IV makes the enzyme more acidic. This may reduce enzyme activity and obstruct access to immunoreactive epitopes and so reduce immunohistochemical staining and immunoassay concentrations.

Hypersialylated DPP IV has been recog nized in rheumatoid arthritis and systemic lupus erythe matosus. Lower activities of plasma sCD26DPP IV in lupus were correlated with increased disease activity. The addition of sitagliptin under these circum stances of reduced DPP IV activity would further inhibit DPP IVs peptidolytic Enzastaurin PKC inhibitor function.