Evidence that exogenous but not endogenous norepinephrine activates the presynaptic alpha-2 adrenoceptors on serotonergic nerve endings in the rat hypothalamus.
In superfused rat hypothalamic slices, clonidine, norepinephrine (NE) and 6-fluoronorepinephrine reduced the electrically evoked release of recently taken up [3H]-5-hydroxytryptamine (5-HT). The inhibitory action of these drugs involves the activation of presynaptic alpha-2 adrenoceptors and it was antagonized by the alpha adrenoceptor antagonists phentolamine or RX 781094. In contrast to the facilitating effect of alpha-2 adrenoceptor antagonists on the electrically evoked [3H]NE overflow in rabbit hypothalamic slices, neither phentolamine nor RX 781094 modified the stimulation-evoked release of [3H]-5-HT at concentrations which completely antagonized the inhibitory action of NE, 6-fluoronorepinephrine and clonidine on 5-HT neurotransmission. In the presence of cocaine, which inhibits the neuronal uptake of NE and increases the concentration of this neurotransmitter in the synaptic gap, alpha-2 adrenoceptor antagonists were still unable to modify the electrically evoked release of [3H]-5-HT. It is concluded that presynaptic alpha-2 adrenoceptors present on serotonergic nerve endings in the hypothalamus are not activated by endogenous NE and do not seem to play a physiological role in the regulation of serotonergic neurotransmission. However, presynaptic inhibitory alpha-2 adrenoceptors can be acted upon by exogenous agonists to inhibit 5-HT release. On the other hand, the presynaptic alpha-2 adrenoceptors on noradrenergic nerve terminals in the rabbit and rat hypothalamus are acted upon by released NE because the alpha-2 adrenoceptor antagonists by themselves increase the electrically evoked release of [3H]NE.
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D004147:Dioxins; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D015016:Yohimbine; D012701:Serotonin; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine; D019329:Idazoxan; D010646:Phentolamine