Pharmacological characterization of presynaptic alpha-adrenoceptors in the nucleus tractus solitarii and the cerebral cortex of the rat.
The presynaptic alpha-adrenoceptors mediating inhibition of K+-induced release of [3H]noradrenaline (NA) from superfused slices and synaptosomes obtained from the nucleus tractus solitarii (NTS) region were characterized pharmacologically and compared to those in the cerebral cortex. Clonidine concentration-dependently (pD2 7.80) reduced the K+-induced [3H]NA release from slices and synaptosomes from the nucleus tractus solitarii of both normotensive and spontaneously hypertensive rats; 10(-6) M clonidine inhibited the [3H]NA release induced by 10 mM K+ to 40% of control. This inhibitory effect of clonidine was antagonized by the alpha2-adrenoceptor antagonist yohimbine (10(-7) M), but not by the alpha1-adrenoceptor antagonist prazosin (10(-7) M). The rank order of apparent affinities of agonists for the presynaptic alpha-adrenoceptors mediating inhibition of [3H]NA release from slices of nucleus tractus solitarii induced by 20 mM K+, was: oxymetazoline greater than clonidine greater than adrenaline greater than alpha-methylnoradrenaline greater than noradrenaline much greater than methoxamine. A similar rank order was found for cerebral cortex slices. The rank order of intrinsic activities in both brain regions was found to be: noradrenaline approximately equal to alpha-methylnoradrenaline approximately equal to adrenaline greater than clonidine greater than oxymetazoline much greater than methoxamine. The data indicate that presynaptic alpha-adrenoceptors mediating inhibition of NA release both in the nucleus tractus solitarii and the cerebral cortex belong to the alpha2-type. The presynaptic alpha2-adrenoceptors in the two brain regions appear to be similar both functionally and pharmacologically. It is suggested that these receptors in the nucleus tractus solitarii may play a role in the hypotensive effect of clonidine.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D011188:Potassium; D009638:Norepinephrine