Multiphasic effect of morphine on the release of substance P from rat trigeminal nucleus slices.
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.
Suarez-Roca
H
H
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7455.
Abdullah
L
L
Zuniga
J
J
Madison
S
S
Maixner
W
W
D000818:Animals; D002850:Chromatography, Gel; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000187:drug effects / Q000378:metabolism*
D009292:Narcotic Antagonists; D013373:Substance P; D009270:Naloxone; D009020:Morphine