Quantitative evaluation of the autoinhibitory feedback of release of 5-HT in the caudate nucleus of the rabbit where an endogenous tone on alpha 2-adrenoceptors does not exist.
Slices of caudate nucleus of the rabbit were preincubated with [3H]serotonin [( 3H]5-HT) in the presence of nomifensine, then superfused and twice stimulated electrically. The stimulation-evoked overflow of tritium, representing action potential-induced, exocytotic release of 5-HT, was inhibited concentration-dependently by 5-HT receptor ligands, the potencies of which were compatible with the assumption of a 5-HT1D-like autoreceptor. The inhibitor of the uptake of 5-HT, 6-nitroquipazine, markedly changed the shape of the concentration-response curve of the 5-HT autoreceptor agonist, 5-carboxamido-tryptamine (5-COHT). The maximum effects of the concentration-response curves of 5-COHT and of exogenous 5-HT became more pronounced in the additional presence of the 5-HT autoreceptor antagonists, metitepin or metergoline. Nonlinear regression analysis of these curves was used to estimate the pKd-value of endogenous 5-HT and the 5-HT biophase concentration at the autoreceptor, in the absence and in the presence of 6-nitroquipazine and in the additional presence of metitepin or metergoline. This revealed a highly operative autoinhibitory feedback, via a 5-HT1D type autoreceptor of release of 5-HT in tissue from the caudate nucleus. Also the inhibition by the alpha 2-adrenoceptor agonists, clonidine and UK-14,304, of release of 5-HT was concentration-dependent. There was neither an enhancement of release by rauwolscine, being a 5-HT autoreceptor agonist and alpha 2-adrenoceptor antagonist, in the presence of metitepin, or by the alpha-adrenoceptor antagonist, phentolamine (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Neuropharmakologisches Labor der Neurologischen Universitätsklinik, Freiburg, Fed. Rep. Germany.
T J
TJ
Feuerstein
A
A
Lupp
G
G
Hertting
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism*; D018492:Dopamine Antagonists; D004558:Electric Stimulation; D005246:Feedback / Q000502:physiology*; D066298:In Vitro Techniques; D008024:Ligands; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1; D012701:Serotonin / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018492:Dopamine Antagonists; D008024:Ligands; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D012701:Serotonin; D009638:Norepinephrine; D010646:Phentolamine