Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions - PubMed (original) (raw)

Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions

H M Chang et al. Anesthesiology. 1989 Apr.

Abstract

An in vitro model system for analysis of presynaptic inhibitory actions of spinal opioids has been applied. Embryonic sensory neurons derived from chick dorsal root ganglia were grown in primary cell culture, and the release of substance P was evoked by electrical field stimulation during exposure to drugs with well-demonstrated affinity for opioid receptors. This allowed a pharmacologic characterization of the inhibitory actions of specific opioid agonists on the release of substance P as measured by radioimmunoassay (RIA). Sufentanil (0.5 microM), a high affinity mu receptor agonist, U-50,488H (25 microM), a selective kappa receptor agonist, and morphine (10 microM), an agonist with high affinity for mu and delta receptors, inhibited the evoked release of substance P by approximately 60%, 40%, and 50%, respectively. For sufentanil the response was demonstrated to be dose-dependent. As is the case for its analgesic action in vivo, morphine was approximately 50-fold less potent than sufentanil on a molar basis in this assay. The actions of sufentanil, U-50-488H and morphine were mimicked by the endogenous opioid peptide met-enkephalin, and its stable synthetic analog D-ala2-met5-enkephalinamide (DAME). Naloxone (25 microM), an opioid receptor antagonist, blocked the inhibitory action of sufentanil (0.5 microM), morphine (5 microM), and DAME (5 microM), but not U-50,488H (10 microM). The action of U-50,488H was partially blocked by the antagonist naltrexone (25 microM). Stereo-selectivity of agonist action was confirmed by the failure of dextrorphan (50 microM), an inactive opioid isomer, to inhibit the release of substance P.(ABSTRACT TRUNCATED AT 250 WORDS)

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Figures

FIG. 1.

Substance P release during three phases of electrical field stimulation: Diagrams showing the result of a typical experiment. Nine cultures from a single plating were divided into three groups of three as shown in table 1. Each culture was stimulated for 3 min at 1 Hz. Baseline (shaded bars) and evoked (blanked bars) levels of substance P immunoreactivity were determined by direct RIA of the release buffer for three repeated phases of stimulation. S1, 2, and 3 stand for the amount of substance P released in Phases 1, 2, and 3, respectively. The upper diagram shows results for the external control group. In the absence of any drug, the amount of evoked substance P release was not significantly different for the three repeated phases. The middle diagram shows the result of the agonist-treated (sufentanil 0.5 µ

) group. The presence of sufentanil during Phase 2 inhibited the evoked substance P release by 54% (P < 0.05) as compared with Phase 1 and 3 of the same group. The lower diagram shows the result of the agonist/antagonist-treated (sufentanil 0.5 µ

and naloxone 25 µ

) group. Naloxone completely blocked the inhibitory effect of sufentanil. Error bars indicate the mean ± SD (n = 3) for released substance P as determined for three cultures of a single group.

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Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions - PubMed (original) (raw)