KH Ko, M Jo, K McCracken and KC Kim
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore 21201, USA.

Extracellular nucleotides stimulate mucin release by binding to the P2u receptor coupled to phospholipase C via G proteins (Br. J. Pharmacol. 103:1053-1056, 1991; Am. J. Respir. Cell Mol. Biol. 8:121-125, 1993). In the present study, we intended to investigate pathways downstream to the phospholipase C activation which is responsible for adenosine triphosphate (ATP)-induced mucin release in hamster tracheal epithelial cells in primary culture. We have found that: (1) Ca2+ ionophores (A23187 and ionomycin) did not affect mucin release even at 1 microM; (2) thapsigargin (10 microM), either alone or in combination with ATP (20 microM), did not enhance mucin release over its respective control group; (3) pretreatment of hamster tracheal surface epithelial (HTSE) cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid- acetoxymethyl ester (BAPTA-AM) (50 microM) did not inhibit ATP-induced mucin release; (4) 4beta-phorbol 12alpha-myristate 13-acetate (PMA, 1 microM) stimulated mucin release and its effect was completely blocked by protein kinase C inhibitors such as sphingosine (10 microM) and calphostin C (0.1 microM), whereas ATP-induced mucin release was blocked, only in part, by these inhibitors; (5) desensitization of protein kinase C by pretreatment with PMA inhibited the PMA-induced mucin release completely, however, ATP-induced mucin release was inhibited only partially. We conclude that mucin release by ATP does not require an increase in the intracellular Ca2+ level but involves the activation of protein kinase C. The results also suggest the presence of another mechanism separate from the phospholipase C-protein kinase C pathway for the ATP-induced mucin release.

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