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Morphine and Enkephalins Potently Inhibit [ 3 H]Noradrenaline Release from Rat Brain Cortex Synaptosomes: Further Evidence for a Presynaptic Localization of μ‐Opioid Receptors
Author(s) -
Mulder Arie H.,
Hogenboom Francois,
Wardeh George,
Schoffelmeer Anton N. M.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05624.x
Subject(s) - dadle , chemistry , agonist , (+) naloxone , enkephalin , δ opioid receptor , synaptosome , endocrinology , opioid receptor , medicine , μ opioid receptor , receptor , opioid , biochemistry , biology , in vitro
Synaptosomes prepared from rat cerebral cortex and labeled with [ 3 H]noradrenaline (NA) were superfused with calcium‐free Krebs‐Ringer‐bicarbonate medium and exposed to 10 m M K + plus 0.1 m M Ca 2+ so that [ 3 H]NA release was induced. 6,7‐Dihydroxy‐ N,N ‐dimethyl‐2‐ami‐notetralin (TL‐99) strongly inhibited synaptosomal K + ‐in‐duced [ 3 H]NA release (EC 50 = 5–10 n M ) by activating α 2 ‐adrenoceptors. Release was also inhibited (maximally by 40–50%) by morphine (EC 50 = 5–10 n M ), [Leu 5 ]enkephalin (EC 50 =∼300 n M ), [d‐Ala 2 ,d‐Leu 5 ]enkephalin (DADLE), and Tyr‐d‐Ala‐Gly‐(NMe)Phe‐Gly‐ol (DAGO) (EC 50 values =∼30 n M ). In contrast to the μ‐selective opioid receptoragonists morphine and DAGO, the highly δ‐selective agon ist [d‐Pen 2 , dPen 5 ]enkephalin (1 μ M ) did not affect [ 3 H]‐NA release. Furthermore, the inhibitory effect of DADLE, an agonist with affinity for both δ‐and μ‐opioid receptors, was antagonized by low concentrations of naloxone. The findings strongly support the view that, like α 2 ‐adrenocep‐tors, μ‐opioid receptors mediating inhibition of NA release in the rat cerebral cortex are localized on noradrenergic nerve terminals.