Cholecystokinin-8 induces intracellular calcium signaling in cultured myenteric neurons from neonatal guinea pigs

The responsiveness of cultured myenteric neurons to cholecystokinin (CCK-8) was examined using fura-2-based digital microfluorimetric measurement of intracellular calcium (Ca(2+)](i)). CCK-8 (10(-10)-10(-6)M) evoked concentration-dependent increases in percentage of neurons responding (8-52%) and deltaCa(2+)](i) (76-169 nM). Gastrin (1 microM) also induced an increase in Ca(2+)](i) in 29+/-6% of neurons (deltaCa(2+)](i): 71+/-3 nM). L-364,718, an antagonist for the CCK-A receptor, blocked Ca(2+)](i) response to CCK-8. Removal of extracellular calcium eliminated CCK-induced Ca(2+)](i) increments, as did the addition of the calcium channel inhibitors nickel (1mM) and lanthanum (5mM). Nifedipine (1-50 microM) dose-dependently attenuated CCK-caused Ca(2+)](i) responses. CCK evokes Ca(2+)](i) signaling in myenteric neurons by the influx of extracellular calcium, likely through L-type calcium channels.