Inhibition by 5,6-dihydroxy-2-dimethylaminotetralin (M7) of noradrenergic neurotransmission in the rabbit hypothalamus: role of alpha-2 adrenoceptors and of dopamine receptors.
Rabbit hypothalamic slices were prelabeled with [3H]norepinephrine and transmitter release elicited by electrical stimulation. In the presence of 10 microM cocaine and in a low Ca++ medium (0.65 mM), exposure for 8 min to exogenous dopamine (0.01-1 microM) inhibited, in a concentration-dependent manner, the electrically evoked release of [3H]norepinephrine. This inhibitory effect of dopamine on [3H]norepinephrine release was antagonized by the dopamine receptor antagonist S-sulpiride (1 microM), but remained unchanged in the presence of the alpha-2 adrenoceptor antagonists idazoxan (1 microM) or yohimbine (0.1 microM). These results indicate that, in a low Ca++ medium, exposure to dopamine decreased [3H]norepinephrine overflow in rabbit hypothalamic slices through the exclusive activation of presynaptic inhibitory dopamine receptors. M7 (5,6-dihydroxy-2-dimethylaminotetralin) is a potent agonist at central presynaptic dopamine autoreceptors and at peripheral alpha-2 adrenoceptors. Exposure to M7 in a normal Ca++ medium, inhibited in a concentration-dependent manner the electrically evoked release of [3H]norepinephrine without affecting the spontaneous outflow of radioactivity. The slope of the concentration-effect curve for these inhibitory effects of M7 was rather flat and the maximal inhibition obtained was 80%. The selective D2 receptor antagonist S-sulpiride (1 microM) failed to produce a significant shift to the right in the concentration-effect curve for the inhibitory effects of M7 on [3H]norepinephrine release. The preferential alpha-2 adrenoceptor antagonist yohimbine (0.1 microM) significantly antagonized the inhibition of [3H]norepinephrine release elicited by 0.01 microM M7, but not for higher concentrations of this aminotetraline.(ABSTRACT TRUNCATED AT 250 WORDS)
Galzin
A M
AM
Langer
S Z
SZ
D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D004357:Drug Synergism; D007031:Hypothalamus / Q000502:physiology*; D019329:Idazoxan; D066298:In Vitro Techniques; D009284:Naphthols / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D004146:Dioxanes; D018492:Dopamine Antagonists; D009284:Naphthols; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D015016:Yohimbine; C009957:5,6-dihydroxy-2-dimethylaminotetralin; D013469:Sulpiride; D004298:Dopamine; D009638:Norepinephrine; D019329:Idazoxan