Characterization of Opioid Receptors Modulating Noradrenaline Release in the Hippocampus of the Rabbit
- 1 June 1986
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 46 (6), 1802-1810
- https://doi.org/10.1111/j.1471-4159.1986.tb08499.x
Abstract
Noradrenaline (NA) release and its modulation via presynaptic opioid receptors were studied in rabbit hippocampal slices, which were preincubated with [3H]NA, continuously superfused in the presence of 30 μM cocaine and stimulated electrically. The evoked release of [3H]NA was strongly reduced by the preferential K-agonists ethylketocyclazocine, dynorphin A1-13, dynorphin A, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U-50,488), and (–)-5,9-dimethyl-2′-OH-2-tetrahydrofurfuryl-6,7-benzomorphan [(–)-MR 2034], whereas (+)-MR 2035 [the (+)-enantiomer of (–)-MR 2034] was ineffective. In contrast, the preferential δ-agonists Leu-enkephalin, Met-enkephalin, and D-Ala2,-D-Leu5-enkephalin (DADLE) as well as the μ-agonists morphine, normorphine, D-Ala2Gly-ol5-enkephalin (DAGO), and β-casomorphin1-4 amide (morphiceptin) were much less potent. However, in similar experiments on rat hippocampal slices DAGO (1 μM) was much more potent than ethylketocyclazocine (1 μM) or DADLE (1 μM). (–)-N-(3-furylmethyl)-α-noretazocine [(–)-MR 2266], 1 μM, a preferential K-antagonist, antagonized the effect of ethylketocyclazocine more potently than (–)-naloxone or (+)-MR 2267 [the (+)-enantiomer of (–)-MR 2266]. Given alone, (–)-MR 2266 slightly and (+)-MR 2267 (1 μM each) greatly enhanced NA release, apparently due to α2-adrenoceptor blockade since their effects were completely abolished in the presence of yohimbine (0.1 μM). The effects of DADLE (1 μM) and DAGO (1 μM) were also antagonized by (–)MR 2266 (0.1 μM) but not by the δ-antagonist N,N-diallyl-Tyr-Aib-Phe-Leu-OH (ICI 174864), 0.3 μM. It is concluded that NA release in the rabbit hippocampus is inhibited via K-receptors; our results do not support the presence of modulatory μ- and δ-receptors in this tissue. However, in the rat hippocampus μ-receptors may modulate NA release.Keywords
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