title: Alpha 2-adrenoceptor mediated inhibition of the release of radiolabelled 5-hydroxytryptamine and noradrenaline from slices of the dorsal region of the rat brain.
abstract: Possible local interactions between noradrenergic and serotonergic systems in the dorsal raphe region of the rat were investigated by studying the effects of various drugs on depolarization (20 mmol/l K+)-induced release of [3H]5-hydroxytryptamine (5-HT) and [3H]noradrenaline (NA) in vitro using a superfusion method. Exogenous 5-HT did not influence the release of [3H]NA. However, NA (in the presence of 10 mumol/l desipramine) as well as the selective alpha 2-adrenoceptor agonists clonidine and oxymetazoline strongly inhibited [3H]5-HT release. The selective alpha 1-adrenoceptor agonists phenylephrine and methoxamine did not affect the release of either [3H]5-HT or [5H]NA. The inhibition by NA of both [3H]5-HT and [3H]NA release was not affected by the beta-adrenoceptor antagonist sotalol nor by the selective alpha 1-adrenoceptor antagonist prazosin. However, phentolamine and the selective alpha 2-adrenoceptor antagonists yohimbine and rauwolscine competitively antagonized the inhibitory effect of NA on [3H]NA release (respective pA2-values 7.5 and 8.3) and on [3H]5-HT release (respective pA2-values 7.7 and 8.2). Moreover, the release of [3H]NA and also, but to a lesser extent, that of [3H]5-HT were increased by the antagonists. It is concluded that the release of both 5-HT and NA in the dorsal raphe region may be subject to presynaptic inhibition by NA via activation of alpha 2-adrenoceptors.
authors.affiliation: Department of Pharmacology, Medical Faculty, Free University, Amsterdam, The Netherlands.
authors.forename: A L
authors.initials: AL
authors.lastname: Frankhuijzen
authors.forename: G
authors.initials: G
authors.lastname: Wardeh
authors.forename: F
authors.initials: F
authors.lastname: Hogenboom
authors.forename: A H
authors.initials: AH
authors.lastname: Mulder
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012701:Serotonin; D011188:Potassium; D009638:Norepinephrine; D010646:Phentolamine