CORTICOTROPIN-RELEASING HORMONE EXCITES MYENTERIC NEURONS IN THE GUINEA-PIG SMALL-INTESTINE

The electrophysiological actions of corticotropin-releasing hormone (CRH) on myenteric neurons from the guinea-pig ileum were studied by intracellular microelectrode recording. CRH, when applied by micropressure ejection or in the medium (0.2-20 nM) evoked prolonged depolarization in 21 of 42 S/type 1 neurons and in 28 of 40 AH/type 2 neurons. These responses were associated with increased input resistance and augmented excitability. The post-spike hyperpolarization in AH/type 2 cells was suppressed during the CRH-evoked responses. The reversal potential of the response to CRH was about - 90 mV, consistent with the closure of potassium channels by the peptide. The CRH-induced depolarization was prevented by incubation in 10-mu-M 5'-N-ethylcarboxamidoadenosine (NECA, an adenosine analog) suggesting that the response was mediated by stimulation of adenylate cyclase and elevation of cAMP. CRH reduced the amplitude of fast nicotinic excitatory postsynaptic potentials. This appeared to be a postsynaptic action because the peptide also reduced the responses to exogenously applied acetylcholine. These results suggest that CRH can directly influence intestinal function by acting on myenteric neurons.