The relationship between secretion of respiratory mucous glycoprotein from feline airways in organ culture and the intracellular activation of protein kinase C (PKC) has been studied using a variety of PKC activators including phorbal myristrate acetate, mezerin and O-A-G as well as inhibitors including W-7 and H-7. PMA and Mezerin have a profound stimulatory effect on acid precipitable glycoprotein release. This effect is partially inhibited by H-7. The PMA effect is also partially inhibited by the PKC inhibitor sphinganin. It is also partially by the lipoxygenase pathway inhibitor NDGA or by the 5 lipoxygenase inhibitor L651.392. It is hoped that these studies will aid in the understanding of receptor-secretion coupling and provide insights into how to limit stimulated secretion in human airways. This project is currently being expanded to investigate cellular mechanisms of secretion using a respiratory epithelial cell line.