Presynaptic inhibitory dopamine receptors on noradrenergic nerve terminals: analysis of biphasic actions of dopamine and apomorphine on the release of endogenous norepinephrine in rat hypothalamic slices.
Electrical field stimulation (5 Hz)- or high K+ (20 mM)-evoked release of endogenous norepinephrine from superfused rat hypothalamic slices in the presence of cocaine (20 microM) was measured by high-performance liquid chromatography with an electrochemical detector. Apomorphine (10-1000 nM) dose-dependently facilitated the electrically evoked release. Apomorphine (1 microM)-induced facilitation was abolished by pretreatment with yohimbine (100 nM), was converted to inhibition by yohimbine (1 microM), but was not antagonized by propranolol (300 nM). Epinephrine (100 nM) decreased the electrically evoked release and the decrease was antagonized by yohimbine (100 nM) and by apomorphine (100 nM), but not by S-sulpiride (100 nM). In the presence of yohimbine (1 microM), apomorphine (10-1000 nM) dose-dependently inhibited the electrically evoked release. Furthermore, in the presence of tetrodotoxin (300 nM), apomorphine (100 nM) also decreased the high K+-evoked release and this decrease was antagonized by S-sulpiride (100 nM). Dopamine produced biphasic actions on the electrically evoked release, a dose-dependent decrease at 30 and 100 nM and an increase at 300 and 1000 nM. Dopamine (300 nM)-induced increase was antagonized by propranolol (300 nM) but not by yohimbine (100 nM). The dopamine (100 nM)-induced decrease was antagonized by S-sulpiride (1 nM), but not by the R-isomer. S-sulpiride (10 to 100 nM) alone dose-dependently increased the electrically evoked release, whereas the R-isomer had no effect. Haloperidol (100 nM) also increased the electrically evoked release.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D014316:Tritium; D015016:Yohimbine; D013469:Sulpiride; D011433:Propranolol; D003042:Cocaine; D001058:Apomorphine; D011188:Potassium; D004298:Dopamine; D009638:Norepinephrine