Opioid-receptor-mediated inhibition of [3H]dopamine but not [3H]noradrenaline release from rat mediobasal hypothalamus slices.
The modulation of the electrically evoked release of [3H]dopamine (DA) and [3H]noradrenaline (NA) by opioid receptor activation was examined in superfused slices of rat mediobasal hypothalamus (MBH). [3H]DA release was inhibited (maximally by 30-35%) by both the selective kappa-agonist U 50,488 (1 nM to 1 microM) and the selective mu-agonist DAGO (0.01-1 microM) but not by the delta-selective agonist DPDPE (1 microM). Naloxone partly antagonized the inhibitory effect of U 50,488 and completely that of DAGO, whereas the selective kappa-antagonist norbinaltorphimine (nor-BNI) only antagonized the inhibition caused by U 50,488. The dopamine D2 receptor agonist quinpirole as well as the alpha 2-adrenoceptor agonist oxymetazoline both decreased (by 25-30%) the evoked overflow of [3H]DA. The evoked release of [3H]NA was not modulated by any of the opioid agonists nor by quinpirole. However, the alpha 2-adrenoceptor agonist oxymetazoline inhibited the release of [3H]NA by 30-40%. Activation of alpha 2-adrenoceptors by oxymetazoline prevented the inhibitory effect of U 50,488, but not DAGO, on evoked [3H]DA release, whereas the selective kappa-antagonist nor-BNI antagonized the inhibition by oxymetazoline of [3H]DA, but not [3H]NA, release. In conclusion, activation of both kappa- and mu-opioid receptors results in an inhibition of evoked DA release from MBH slices but does not modulate NA release. Therefore, several of the reported effects of opioids on hormone secretion may be an (indirect) consequence of a reduction of DA release.(ABSTRACT TRUNCATED AT 250 WORDS)
Heijna
M H
MH
Department of Pharmacology, Medical Faculty, Free University, Amsterdam, The Netherlands.
Padt
M
M
Hogenboom
F
F
Schoffelmeer
A N
AN
Mulder
A H
AH
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009638:Norepinephrine / Q000378:metabolism*; D010109:Oxymetazoline / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D004873:Ergolines; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019257:Quinpirole; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D010109:Oxymetazoline; D004298:Dopamine; D009638:Norepinephrine