Electrophysiological and autoradiographical evidence for cholecystokinin A receptors on rat isolated nodose ganglia

The sulphated octapeptide, cholecystokinin (CCK-8S), is believed to be a neurotransmitter of vagal sensory neurones, and here the presence of functional receptors for CCK-8S in the rat vagus nerve has been investigated by electrophysiological and autoradiographic techniques. CCK-8S caused concentration-dependent depolarizations when superfused over the rat isolated nodose ganglion at 37°C as measured by a silicone grease gap technique. Concentration-response curves to CCK-8S were shifted to the right by low concentrations of the CCK A receptor antagonist, Devazepide, but not by the CCK B receptor antagonist, L-365,260, data which indicate that receptors were of the CCK A subtype. Consistent with this notion, the CCK B agonist, unsulphated CCK-8, was without effect until high concentrations (> 1 μM) were used. A synthetic analogue of CCK-8S, d-Tyr 25(Nle 28,31)-CCK 25–33S, which has been reported to be more stable and peptidase-resistant than CCK-8S, was equipotent with CCK-8S in depolarizing the nodose ganglion. When d-Tyr 25(Nle 28,31)-CCK 25–33S was labelled with 125I, it bound to tissue sections of nodose ganglion. By light microscopic autoradiography, silver grains were found to be highly localized over cell bodies of vagal sensory neurones. An excess of CCK-8S inhibited binding as did Devazepide, but not L-365,260, confirming that binding sites were CCK A subtype receptors. These results indicate the existence of functional CCK A receptors in the nodose ganglion and strengthen the case for the involvement of vagal sensory neurones in gastric emptying and satiety.