ACTION OF CHOLECYSTOKININ OCTAPEPTIDE AND CCK-RELATED PEPTIDES ON NEURONS IN INFERIOR MESENTERIC GANGLION OF GUINEA-PIG

  • 1 November 1986
    • journal article
    • research article
    • Vol. 239  (2) , 618-625
Abstract
The effect of cholecystokinin octapeptide (CCK8) on neurons of inferior mesenteric ganglion of the guinea pig was examined with intracellular microelectrodes. CCK8 nonsulfated pressure ejected from micropipettes resulted in a depolarization of 95% of neurons tested. The ED50 for depolarization was 1.1 .+-. S.D. 0.5 pmol. The maximum depolarization averaged 9.3 mV (.+-. S.D. 6.1 mV) and lasted for 99.7 sec (.+-. S.D. 14.6 sec). In 73% of the cells the depolarization was associated with either an increase or a decrease in the cell input resistance; the remainder depolarized without a change in input resistance. In those cells in which the input resistance decreased during depolarization (59% of cells tested), the null potential was -36.3 .+-. 9.3 mV. In those cells in which the input resistance increased during depolarization (20% of cells tested), the null potential was -103 .+-. 6 mV. In those cells that depolarized without a change in input resistance (21% of cells tested) the null potential was -90.4 .+-. 2.3 mV. At an equal dose, the sulfated form of CCK8 resulted in a depolarization that was 47% (.+-.26%) smaller in amplitude and 27% (.+-.21%) shorter in duration than the depolarization produced by the nonsulfated form of CCK8. The effects of both forms of CCK8 were not abolished in low calcium-high magnesium, suggesting a direct action on the postsynaptic membrane. Application of CCK8 at intervals less than 10 min resulted in marked desensitization of the response. Desensitization to CCK8 reduced by 52% (.+-.9%) the amplitude of the nerve-evoked slow excitatory postsynaptic potential in 67% of cells in which it was tested. Tetrodotoxin (3 .mu.M) or low sodium medium (11.9 mM) depressed slightly the amplitude of CCK8-induced depolarization, indicating some dependence of CCK8 action on the activation of sodium conductance. Elevated potassium (23.8 mM) attenuated the CCK depolarizations by an average of 60%. CCK4, CCK7, cerulein and gastrin all evoked similar depolarizations in 93% of cells tested. These results demonstrate that CCK8 and CCK-related peptides have an excitatory action on neurons in the inferior mesenteric ganglion of the guinea pig and because CCK-line immunoreactivity is localized in fibers within this ganglion, these peptides are candidate neurotransmitters for the slow excitatory postsynaptic potential.