Effects of Different Opioid Receptor Antagonists on the Electrically-Evoked Release of Endogenous Dopamine from the Isolated Neural Lobe of the Rat Pituitary Gland in vitro.
Abstract Isolated neural lobes of the rat pituitary gland were incubated in Krebs-HEPES solution which contained the dopamine uptake inhibitor GBR 12921 and in some experiments additionally pargyline. The release of endogenous dopamine evoked by electrical stimulation of the pituitary stalk was determined by high-performance liquid chromatography with electrochemical detection. (+/-)- Naloxone increased the evoked dopamine release maximally by 440% (EC(50) 209 nM). The (+)-enantiomer of naloxone (up to 10 muM) did not affect the release of dopamine. The preferential kappa-opioid receptor antagonist MR 2266 increased the evoked dopamine release maximally by 135% (EC(50) 7 nM). MR 2267, the inactive (+)-enantiomer of MR 2266, had no effect on dopamine release. The delta-opioid receptor selective antagonist ICI 174864 increased the release of dopamine maximally by 120% (EC(50) 10 nM). The non-selective opioid receptor agonist etorphine up to 10 muM had no effect on the evoked dopamine release. In conclusion, endogenous opioids in the neurohypophysis strongly inhibit the release of endogenous dopamine from this gland. Activation of kappa- and delta-opioid receptors appears to be involved in the inhibitory action of the endogenous opioids on the neurohypophysial release of dopamine.
Racké
K
K
Pharmakologisches Institut der Universität Mainz, Obere Zahlbacher Str. 67, D-6500 Mainz, FRG.
Hering
B
B
Weber
I
I