D. Burdakov et A. Galione, Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell, CURR BIOL, 10(16), 2000, pp. 993-996
Bombesin and cholecystokinin (CCK) peptides act as signalling molecules in
both the central nervous system and gastrointestinal tract [1-4]. It was re
ported recently that nicotinic acid adenine dinucleotide phosphate (NAADP)
releases Ca2+ from mammalian brain microsomes [5] and triggers Ca2+ signals
in pancreatic acinar cells, where it is proposed to mediate CCK-evoked Ca2
+ signals [6]. Here, for the first time, we have finely resolved bombesin-i
nduced cytosolic Ca2+ oscillations in single pancreatic acinar cells by who
le-cell patch-clamp monitoring of Ca2+-dependent ionic currents [6-8]. Pico
molar concentrations of bombesin and CCK evoked similar patterns of cytosol
ic Ca2+ oscillations, but high, desensitising, NAADP concentrations selecti
vely inhibited CCK, but not bombesin-evoked signals. Inhibiting inositol tr
isphosphate (IP3) receptors with a high concentration of caffeine blocked b
oth types of oscillations. We further tested whether NAADP is involved in C
a2+ signals triggered by activation of the low-affinity CCK receptor sites.
Nanomolar concentrations of CCK evoked non oscillatory Ca2+ signals, which
were not affected by desensitising NAADP receptors. Our results suggest th
at Ca2+-release channels gated by the novel Ca2+ mobilising molecule NAADP
are only essential in specific Ca2+-mobilising pathways, whereas the IP3 re
ceptors are generally required for Ca2+ signals. Thus, the same cell may us
e different combinations of intracellular Ca2+-releasing messengers to enco
de different external messages.