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Mucin secretion and PKC isoforms in SPOC1 goblet cells: differential activation by purinergic agonist and PMA

¹Cystic Fibrosis/Pulmonary Treatment and Research Center; and ²Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599-7248

Submitted 28 October 2002 ; accepted in final form 10 February 2003

SPOC1 cells, which are a mucin-secreting model of rat airway goblet cells, possess a luminal P2Y₂ purinoceptor through which UTP, ATP, and ATPS stimulate secretion with EC₅₀ values of 3 µM. PMA elicits mucin secretion with high EC₅₀ (75 nM) and saturation (300 nM) values. For the first time in airway mucin-secreting cells, the PKC isoforms expressed and activated by a secretagogue were determined using RT-PCR/restriction-enzyme mapping and Western blotting. Five isoforms were expressed: cPKC, nPKC and -, and aPKC and -/. PMA caused cPKC and nPKC to translocate to the membrane fraction of SPOC1 cells; only nPKC so responded to ATPS. Membrane-associated nPKC and mucin secretion increased in parallel with ATPS concentration and yielded EC₅₀ values of 2–3 µM and maximum values of 100 µM. Effects of PMA to increase membrane-associated cPKC and nPKC saturated at 30 nM, whereas mucin secretion saturated at 300 nM, which suggests a significant PKC-independent effect of PMA on mucin secretion. A prime alternate phorbol ester-receptor candidate is the C1-domain protein MUNC13. RT-PCR revealed the expression of ubiquitous (ub)MUNC13-2 and its binding partner, DOC2-. Hence, P2Y₂ agonists activate nPKC in SPOC1 cells. PMA activates cPKC and nPKC at high affinity and stimulates a lower affinity PKC-independent pathway that leads to mucin secretion.

exocytosis; mucus; airways; P2Y receptor

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