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 o f functional receptors for CCK-8S in the rat vagus nerve has been inve stigated by electrophysiological and autoradiographic techniques. CCK- 8S caused concentration-dependent depolarizations when superfused over the rat isolated nodose ganglion at 37 degrees C as measured by a sil icone grease gap technique. Concentration-response curves to CCK-8S we re shifted to the right by low concentrations of the CCK, receptor ant agonist, Devazepide, but not by the CCK, receptor antagonist, L-365,26 0, data which indicate that receptors were of the CCKA subtype. Consis tent with this notion, the CCK, agonist, unsulphated CCK-8, was withou t effect until high concentrations (>1 mu M) were used. A synthetic an alogue of CCK-8S, D-Tyr(25)(Nle(28,31))-CCK 25-33S, which has been rep orted to be more stable and peptidase-resistant than CCK-8S, was equip otent with CCK-8S in depolarizing the nodose ganglion. When D-Tyr(25)( Nle(28,31))-CCK 25-33S was labelled with I-125, it bound to tissue sec tions of nodose ganglion. By light microscopic autoradiography, silver grains were found to be highly localized over cell bodies of vagal se nsory neurones. An excess of CCK-8S inhibited binding as did Devazepid e, but not L-365,260, confirming that binding sites were CCK, subtype receptors. These results indicate the existence of functional CCK, rec eptors in the nodose ganglion and strengthen the case for the involvem ent of vagal sensory neurones in gastric emptying and satiety.