The modulation of [3H]noradrenaline and [3H]serotonin release from rat brain synaptosomes is not mediated by the alpha 2B-adrenoceptor subtype.
The present study aimed at relating the presynaptic alpha 2-adrenoceptors, known to modulate noradrenaline and serotonin release, with the recently described alpha 2A- and alpha 2B-adrenoceptor subtypes. The effects of the agonist oxymetazoline (selective for alpha 2A subtype) and of three adrenoceptor antagonists (idazoxan, 1-(2-pyrimidinyl)piperazine (PmP) and prazosin, the last one known to be alpha 2B selective) were evaluated on [3H]noradrenaline and [3H]serotonin release in superfused synaptosomes from rat brain cortex. These drugs were also tested in [3H]yohimbine binding to human platelet membranes (containing only alpha 2A receptors) and to neonatal rat lung membranes (containing only alpha 2B receptors). The affinity pattern of these compounds at alpha 2A-adrenoceptors in binding studies was oxymetazoline greater than = idazoxan greater than PmP greater than prazosin; at alpha 2B-adrenoceptors it was idazoxan greater than = prazosin greater than PmP = oxymetazoline. Oxymetazoline inhibited with high and similar potencies the K(+)-evoked [3H]noradrenaline and [3H]serotonin release, IC50 18 and 7 nM, respectively; in the same conditions, the IC50 values of noradrenaline were 42 and 168 nM, respectively. The antagonist affinity pattern (antagonism against noradrenaline) was idazoxan greater than PmP greater than prazosin, either on [3H]serotonin release. These results indicate that presynaptic alpha 2 auto- or heteroreceptors do not belong to the alpha 2B subtype and suggest that the modulation of noradrenaline and serotonin release may be mediated by the alpha 2A-adrenoceptor subtype.
Gobbi
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Frittoli
E
E
Mennini
T
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D009638:Norepinephrine