CCK_A receptors mediate slow depolarizations in cultured mammalian sympathetic neurons

The effect of cholecystokinin octapeptide (CCK-8) was examined in guinea-pig celiac ganglion (CG) neurons in primary culture using standard intracellular recording techniques. Sulfated CCK-8 (CCK-8S; 1 μM) evoked slow depolarizing responses in 94% of CG neurons tested. In contrast, membrane potential was not affected by nonsulfated CCK-8 (CCK-8NS; 1 μM), CCK tetrapeptide (CCK-4; 1 μM), or gastrin (1 μM). The selective CCK_A receptor antagonist L 364,718 potently inhibited CCK-8S-induced slow depolarizations(IC₅₀ 2.9 pM). In contrast, the selective CCK_B receptor antagonist L 365,260 was a weak inhibitor of CCK-8S-induced slow depolarizations (IC₅₀ 1.3 μM). The depolarizing responses to CCK-8S were associated with an average increase in cell input resistance of 61%. Single electrode voltage clamp experiments indicated that CCK-8S-induced depolarizations were associated with a slow inward shift in holding current. Thus, the present findings indicate that guinea-pig cultured CG neurons are endowed with excitatory CCK_A receptors the activation of which elicits a decrease in membrane conductance, thereby resulting in slow depolarizations.