T. Kanno et al., RECURRENT CA2-CELLS( SPIKES AS INTRACELLULAR SIGNALS FOR PHYSIOLOGICAL SECRETORY RESPONSES IN PANCREATIC ACINAR), Biomedical research, 15, 1994, pp. 45-49
Analysis of competitive inhibition of tracer binding by unlabeled CCK-
8 was consistent with binding to two affinity states of CCK receptor o
n isolated rat pancreatic acini, with the equilibrium dissociation con
stants for the high- and low-affinity states equal to 15.2 pM and 3.5
nM respectively. Spatial and temporal dynamics of cytosolic concentrat
ion of Ca2+, [Ca2+]c, were recorded by a digital image analyzing techn
ique using Fura-2 Continuous stimuration of isolated acini with a phys
iological concentration of cholecystokinin octapeptide (10 pM CCK-8) c
aused recurrent Ca2+ spikes and a sustainable amylase output. These re
sponses were both abolished in Ca2+-deficient environment. The stimula
tion of the acini with a pharmacological (100 pM) concentration, howev
er, induced a rapid [Ca2+]c increase followed by a gradual decay, and
a rapid initial rise in amylase output followed by a gradual decay. In
the Ca2+-deficient environment, the initial phases of responses remai
ned but the second decay phases were selectively abolished. These resu
lts indicate that the binding of CCK-g to the high-affinity state on t
he acini induces recurrent Ca2+ spikes, which may maintain the sustain
able secretory responses in the pancreatic acinar cells.