Effects of cholecystokinin and pentagastrin on rat hippocampal neurones maintained in vitro.

Extracellular and intracellular recordings from CA1 neurones of rat hippocampal slices were undertaken to assess the relative potencies of cholecystokinin fragments. The CCK peptides displayed a large variability in their effects on extracellularly recorded population spikes. Intracellular recordings from CA1 neurones revealed a more consistent excitant action of these compounds. The C-terminal octapeptide CCK-8S, the tetrapeptide CCK-4 and pentagastrin were all found to be agonists when applied to hippocampal CA1 neurones maintained in vitro. Repeated application of the peptide fragments to the same cell resulted in a loss of activity. Neurones pre-treated with a CCK peptide showed no response to an application of a second, different, CCK fragment indicative of receptor cross-desensitization. Depolarisations induced by the excitatory amino acid L-glutamate remained unaffected by peptide application. These data suggest that the CCK fragments are agonists at rat CA1 neurones and share a common mode of action distinct from that of the excitatory amino acid L-glutamate.