Excitatory effects of cholecystokinin in rat hippocampus: pharmacological response compatible with ‘central’- or B-type CCK receptors

Abstract

The effects of the sulfated octapeptide of cholecystokinin (CCK 8-S), the non-sulfated homolog (CCK 8-NS) as well as the C-terminal di-, tri- and tetrapeptidic fragments (respectively CCK 2, CCK 3 and CCK 4) were studied in vitro in rat hippocampal slices by extracellular recording of the spontaneous action potential discharge frequency of neurons located in the CA1 stratum pyramidalis. Bath-applied CCK 8-S concentration-dependently increased the action potential discharge frequency of hippocampal CA1-neurons in concentrations ranging from 0.05 to above 1 μM. Both CCK 8-NS and CCK 4 exhibited reversible and concentration-dependent excitatory effects. They were 4 and 10 times less potent than CCK 8-S,respectively, as concentrations of 2μM CCK 8-NS and 5 μM CCK 4 were needed to evoke the same excitation as that induced for a given neuron by 0.5 μM CCK 8-S. In contrast, none of the shorter fragments (CCK 2 and CCK 3) were effective in altering spontaneous discharge of CCK 8-S-sensitive neurons even at concentrations of 100μM. The pharmacologic profile of the excitatory response observed in the rat hippocampus follows the same pattern as the binding profile observed on brain membrane preparations. It is therefore concluded that the CCK receptors involved in this response seem to be related more to the ‘central’- or B-type CCK receptors rather than to the ‘peripheral’- or A-type CCK receptors.