Release-inhibiting alpha 2-adrenoceptors at serotonergic axons in rat and rabbit brain cortex: evidence for pharmacological identity with alpha 2-autoreceptors.
The pharmacological properties of the presynaptic alpha 2-adrenoceptors modulating the release of serotonin in rat and rabbit brain cortex (alpha 2-heteroreceptors) were compared with the properties of presynaptic alpha 2-autoreceptors in the same brain area. Brain cortex slices were preincubated with [3H]-serotonin or [3H]-noradrenaline and then superfused and stimulated by brief high-frequency pulse trains. The alpha 2-adrenoceptor agonist bromoxidine reduced the electrically evoked overflow of tritium in experiments with both [3H]-noradrenaline and [3H]-serotonin and in brain slices from either species. The antagonists phentolamine, idazoxan, (+)-mianserin, rauwolscine, 5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2-ami ne (ORG 20350), 2-(2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane (WB 4101), (-)-mianserin and corynanthine caused parallel shifts of the concentration-inhibition curves of bromoxidine to the right. Negative logarithms of antagonist dissociation constants pKd were calculated from the shifts. In the rat, the alpha 2-autoreceptor pKd value of each single antagonist was similar to its alpha 2-heteroreceptor pKd value, maximal difference 0.4, giving a close correlation, r = 0.97 (P < 0.001). In the rabbit equally, the alpha 2-autoreceptor pKd value of each single antagonist was similar to its alpha 2-heteroreceptor pKd value, maximal difference 0.4, again yielding a close correlation, r = 0.96 (P < 0.001). However, antagonist pKd values at rat alpha 2-autoreceptors differed from those at rabbit alpha 2-autoreceptors, r = 0.70 (P > 0.05), and antagonist pKd values at rat alpha 2-heteroreceptors differed from those at rabbit alpha 2-heteroreceptors, r = 0.64 (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Trendelenburg
A U
AU
Pharmakologisches Institut der Universität, Freiburg, Germany.
Trendelenburg
M
M
Starke
K
K
Limberger
N
N
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects* / Q000502:physiology*; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure*; D000068438:Brimonidine Tartrate; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D005260:Female; D007700:Kinetics; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D014316:Tritium
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D017660:Autoreceptors; D011725:Pyridines; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D013844:Thiazoles; D014316:Tritium; C075282:ORG 20350; D008803:Mianserin; D012701:Serotonin; D000068438:Brimonidine Tartrate; D009638:Norepinephrine