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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Superfusion of slices from the dorsal half of the lumbar enlargement of rat spinal cord with Krebs-Henseleit medium supplemented with 30 μM bacitracin allowed the collection of substance P-like immunoreactive material (SPLI), which was released at a rate of ∼ 10 pg/4 min. Tissue depolarization by an excess of K+ (30–60 mM) or veratridine (50 μM) induced a marked increase in SPLI outflow, provided that Ca2+ was present in the superfusing fluid. K+-or veratridine-induced SPLI overflow could be modulated in opposite directions by μ and δ opioid receptor agonists. Thus, the two preferential μ agonists Tyr-d-Ala-Gly-MePhe-Gly-ol (DAGO; 10 μM) and Tyr-d-Ala-Gly-MePhe-Met(O)5-OH (FK-33824; 0.1 μM) enhanced SPLI overflow from depolarized tissues, whereas the selective δ agonists Tyr-d-Thr-Gly-Phe-Leu-Thr (deltakephalin; 3 μM) and [2-d-penicillamine, 5-d-penicillamine]enkephalin (50 μM) reduced it. The effect of DAGO was antagonized by a low concentration (1 μM) of naloxone but not by the selective δ antagonist ICI-154129 (50 μM). In contrast, the latter drug prevented the inhibitory influence of δ agonists on K+-induced SPLI release. Complementary experiments with morphine (10 μM) and [2-d-alanine, 5-d-leucine]enkephalinamide (3 μM), in combination with 1 μM naloxone or 50 μM ICI-154129 for the selective blockade of μ or δ receptors, respectively, confirmed that the stimulation of μ receptors increased, whereas the stimulation of δ receptors reduced, SPLI overflow. The results suggest that, at the spinal level, the antinociceptive action of δ but not μ agonists might involve a presynaptic inhibition of substance P-containing primary afferent fibers.
    Type of Medium: Electronic Resource
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