CCKA AND CCKB RECEPTOR SUBTYPES BOTH MEDIATE THE EFFECTS OF CCK-8 ON MYENTERIC NEURONS IN THE GUINEA-PIG ILEUM

The effects of cholecystokinin (CCK-8) on myenteric S neurons were inv estigated by intracellular recording techniques, with the aim to deter mine the CCK receptor subtypes involved. CCK-8 (1-1000 nM) evoked conc entration-dependent long-lasting excitatory responses in 45 of 54 neur ons. CCK receptor antagonists were applied to 15 neurons in which CCK- 8 evoked an excitatory response. In 5 of these neurons, application of the CCKA antagonist L-364,718 (100-500 nM) antagonized the action of CCK-8 and the CCKB antagonist L-365,260 (500 nM) had no effect. L-365, 260 (100-500 nM) antagonized the CCK-8 induced response in 5 neurons, on which L-364,718 had no effect. In the other 5 neurons each antagoni st (500 nM) partly inhibited the CCK-8 evoked excitation and applicati on of both antagonists (500 nM) caused a complete blockade of the resp onse to CCK-8. The selective CCKB receptor agonist CCK-8NS had similar excitatory effects as CCK-8, but only on the neurons in which CCK-8 e voked effects were antagonized by L-365,260. The results demonstrate t hat the excitatory effects of CCK-8 are mediated by both CCKA and CCKB receptor subtypes. Further, the results indicate that some neurons po ssess exclusively the CCKA or the CCKB receptor subtype, but others po ssess both subtypes. (C) 1997 Elsevier Science B.V.