Nonopioid mechanism of morphine modulation of the activation of 5-hydroxytryptamine type 3 receptors.

The effect of morphine on the ion current mediated by 5-hydroxytryptamine (5-HT3) receptors was investigated in rat nodose ganglion neurons and in Xenopus oocytes expressing the cloned 5-HT3 receptor. Morphine reversibly inhibited the 5-HT-induced current and shifted the 5-HT concentration-response curve to the right in a parallel fashion, without reducing the maximal 5-HT response. IC50 values for morphine were 0.3 microM in nodose neurons and 0.32 microM in oocytes. The apparent Kd of morphine in nodose neurons was 0.903 microM. This effect of morphine was immediate not dependent on membrane potential, and not prevented by the opioid receptor antagonists naltrexone and beta-chlornaltrexamine. It is concluded that opioid receptors were not involved in the present study and that morphine acted at the agonist recognition site located on the 5-HT3 receptor.