Naloxone-precipitated contractions of the guinea pig ileum made tolerant to a synthetic opioid peptide: evidence against the involvement of capsaicin-sensitive neurones.

In segments of guinea pig ileum made tolerant-dependent to the synthetic opioid peptide [D-Met2,Pro5]enkephalinamide, naloxone (1 microM) caused half-maximal longitudinal contractions. These were strongly reduced by hyoscine or desensitization to serotonin but not by hexamethonium, desensitization to substance P or pretreatment with capsaicin. Contractions of similar size evoked by capsaicin (0.3 microM) in the presence of naloxone were abolished by capsaicin pretreatment, reduced by substance P desensitization or hyoscine but not by desensitization to serotonin. Thus, the two types of contraction clearly have different mechanisms; enteric capsaicin-sensitive neurones or substance P-containing motor neurones seem not to be involved in the naloxone-precipitated contraction while serotonin may play a role in this response.