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Brain Res. 1992 May 8;579(2):187-94.

Multiphasic effect of morphine on the release of substance P from rat trigeminal nucleus slices.

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Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7455.


It is generally accepted that morphine acts presynaptically to inhibit substance P (SP) release from afferent terminals in the trigeminal nucleus. Recent studies, however, provide evidence that opioids produce both inhibitory and excitatory effects on SP release which are concentration- and receptor subtype-dependent. In the present study, we have examined a wide range of morphine concentrations on K(+)-evoked SP release from rat trigeminal nucleus caudalis slices. Immunoreactive SP was measured in perfusates. Morphine produced multiphasic effects on K(+)-evoked SP release without affecting basal release. A very low nanomolar concentration (1 nM) suppressed release, higher nanomolar concentrations (100-300 nM) facilitated release, a low micromolar concentration (3 microM) suppressed release, and a higher micromolar concentration (30 microM) facilitated release. These effects were abolished by opioid receptor blockade with naloxone (30 nM). Thus, morphine produces a complex bi-directional modulation of SP release from TNC which is concentration- and possibly receptor subtype-dependent.

[Indexed for MEDLINE]

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