Quantitative immunocytochemical study of secretory protein expression in parotid glands of rats chronically treated with isoproterenol.

Chronic treatment of mice and rats with isoproterenol (IPR) causes marked hypertrophy and hyperplasia of the salivary glands, and alters the expression of several secretory proteins. We used quantitative postembedding immunogold labeling to study the cellular responses in the rat parotid gland during daily (up to 10 days) injections of IPR and during recovery (up to 14 days) after cessation of IPR treatment. Labeling densities of acinar cell secretory granules with antibodies to amylase and protein SMG-B1 (cross-reactive with the rat homologue of Parotid Secretory Protein, PSP) fell to 10% of control levels after 8-10 IPR injections, then increased during recovery, paralleling previous biochemical determinations of changes in protein and mRNA levels. With antibodies to proline-rich proteins (PRP), labeling densities initially fell, then subsequently showed considerable variability, but never exceeded control levels. These results contrast with biochemical determinations showing a marked induction of PRP synthesis, and may have both immunological and structural explanations. Occasional intercalated duct cells located close to the acini underwent differentiation toward an acinar-like phenotype as a result of IPR treatment. After 1-2 IPR injections, the secretory granules of these cells labeled with antibodies to amylase and PRP. Subsequently, the granules appeared electron-lucent and were increased in size and number. These observations support earlier work, suggesting that intercalated duct cells may differentiate into other gland cell types.