Alpha-adrenoceptor-mediated modulation of 5-hydroxytryptamine release from rat brain cortex slices.
Slices of rat brain cortex preincubated with 3H-5-hydroxytryptamine were superfused with physiological salt solution and stimulated electrically, or they were superfused with Ca2+-free solution containing 25 mM K+ and stimulated by introduction of 1.3 mM CaCl2 for 2 min. 1. The electrically evoked 3H overflow was decreased by noradrenaline and increased by phentolamine in a concentration-dependent manner. 2. Phentolamine caused a parallel shift to the right of the concentration-response curve of noradrenaline for its inhibitory effect on impulse-evoked 3H overflow; by contrast, it left the inhibitory effect of unlabelled 5-hydroxytryptamine on the electrically evoked 3H overflow unaffected. 3. Propranolol did not alter the inhibitory effect of noradrenaline on impulse-induced 3H overflow. 4. The increasing effect of phentolamine on the electrically evoked 3H overflow was not modified by paroxetine. 5. Cocaine (at a concentration which almost completely blocks the uptake of 3H-noradrenaline but only partially that of 3H-5-hydroxytryptamine into cortex slices) decreased impulse-evoked 3H overflow. This effect was abolished by phentolamine. 6. In the presence of tetrodotoxin throughout superfusion, the Ca2+-evoked 3H-overflow from slices superfused with Ca2+-free solution was inhibited by noradrenaline and increased by phentolamine. These findings suggest that the terminal serotoninergic fibers of rat brain cortex possess alpha-adrenoceptors, activation of which by exogenous or endogenous noradrenaline leads to inhibition of the release of 5-hydroxytryptamine.
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D017981:Receptors, Neurotransmitter; D012701:Serotonin; D003042:Cocaine; D009638:Norepinephrine; D010646:Phentolamine