Cholecystokinin octapeptide and gastric mechanoreceptor activity in rat brain

Extracellular unitary recordings were made from neurons in the rat dorsal vagal nucleus, and the response of these neurons to iontophoretically applied cholecystokinin octapeptide (CCK-OP) and proglumide (a novel CCK antagonist) was studied. The effect of CCK-OP and proglumide on the response of the neurons to gastric distension was also studied. Seventy-four percent (n = 39) of the neurons studied were excited by CCK-OP. It was not possible to antagonize the response to CCK-OP with proglumide. CCK-OP was also found to be an effective modulator of the response to gastric distension; the effects were diverse ("on" responses were augmented; "off" and "transient" responses were diminished) but were always the same within each characteristic pattern of response to distension. These results provide supporting evidence for CCK-OP, a peptide common to both brain and gut, acting in the role of a neural modulator in the control of the gastrointestinal tract. It is possible to speculate that the potent effect of CCK-OP on neuronal excitability and on the central representation of gastric mechanoreceptor activity may well substantiate the role of CCK-OP as a central regulator of feeding behavior.