SALIVARY GLAND SECRETORY MECHANISMS DURING NORMAL AND ALTERED FUNCTIONAL STATES

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The health of the oral cavity is maintained by salivary secretions. The principal function of salivary glands is to produce these complex fluids. We have utilized a variety of tools to understand saliva formation and the pathologic processes that alter normal secretory events. During this reporting period, we have concentrated our efforts on an important issue relevant to the development of clinically-applicable gene transfer vectors for use in salivary glands: the relatively short time of transgene expression which we have previously reported occurs with this tissue. We have approached this in three general ways: (i) to understand, and attempt to control, the inflammatory response which occurs following adenovirus administration; (ii) to re-engineer the recombinant vectors to render them more potent, thus allowing lower doses of virus to be used in vivo; and (iii) to evaluate further the use of an adeno-associated viral vector as a gene transfer vehicle (since this virus is able to integrate into the host cell DNA) in place of adenoviral vectors. A related, but separate, major effort has been directed at defining salivary cell type (acinar, ductal)-specific promoters. Their utilization in place of the viral promoters currently employed should enhance considerably vector safety and the stability of gene expression. Further, this work of itself makes fundamental contributions to the biology of salivary glands. Additionally, we have continued the studies that we began last year of the topological "mapping" of key plasma membrane transport proteins, and associated protein routing signals, in salivary cells.