Gastrin and the neuropeptide PACAP evoke secretion from rat stomach histamine-containing (ECL) cells by stimulating influx of Ca2+ through different Ca2+ channels

Erik Lindström, Lena Eliasson, Maria Björkqvist, Rolf Håkanson

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Abstract

Gastrin and PACAP stimulate secretion of histamine and pancreastatin from isolated rat stomach ECL cells. We have examined whether or not secretion depends on the free cytosolic Ca2+ concentration ([Ca2+i) and the pathways by which gastrin and PACAP elevate [Ca2+i. Secretion was monitored by radioimmunoassay of pancreastatin and changes in [Ca2+i by video imaging. The patch clamp technique was used to record whole-cell currents and membrane capacitance (reflecting exocytosis). In the presence of 2 mM extracellular Ca2+, gastrin and PACAP induced secretion and raised [Ca2+i. Without extracellular Ca2+ (or in the presence of La3+) no secretion occurred. The extracellular Ca2+ concentration required to stimulate secretion was 10 times higher for gastrin than for PACAP. Depletion of intracellular Ca2+ pools by thapsigargin had no effect on the capacity of gastrin and PACAP to stimulate secretion. Gastrin-evoked secretion was inhibited 60-80 by L-type channel blockers and 40 by the N-type channel blocker -conotoxin GVIA. Combining L-type and N-type channel blockers did not result in greater inhibition than L-type channel blockers alone. Whole-cell patch clamp measurements confirmed that the ECL cells are equipped with voltage-dependent inward Ca2+ currents. A 500 ms depolarising pulse from -60 mV to +10 mV which maximally opened these channels resulted in an increase in membrane capacitance of 100 fF reflecting exocytosis of secretory vesicles. PACAP-evoked secretion was reduced 40 by L-type channel blockers but was not influenced by inhibition of N-type channels. SKF 96365, a blocker of both L-type and receptor-operated Ca2+ channels, inhibited PACAP-evoked secretion by 85 . Combining L-type channel blockade with SKF 96365 abolished PACAP-evoked secretion. The results indicate that gastrin- and PACAP-evoked secretion depends on Ca2+ entry and not on mobilisation of intracellular Ca2+. While gastrin stimulates secretion via voltage-dependent L-type and N-type Ca2+ channels, PACAP acts via L-type and receptor-operated Ca2+ channels.
Original languageEnglish
Pages (from-to)663-677
JournalJournal of Physiology
Volume535
Issue number3
Publication statusPublished - 2001

Subject classification (UKÄ)

  • Physiology

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