Subtype determination of soma-dendritic alpha2-autoreceptors in slices of rat locus coeruleus.
The aim of the study was to subclassify the soma-dendritic alpha2-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective alpha2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC50 values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 microM) and rauwolscine (0.15 microM) but not by prazosin (1 microM). Apparent Kd values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent Kd values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 microM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC50 values of 120 and 250 nM, respectively. Prazosin (1 microM) again was ineffective. All three antagonist affinity estimates - against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) - yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 microM. These findings identify the soma-dendritic alpha2-autoreceptors of the LC as the rat variant of the alpha2A/D-adrenoceptor, i.e. alpha2D. Not only presynaptic but also soma-dendritic alpha2-autoreceptors may at least predominantly be alpha2A/D throughout the nervous system.
Nörenberg
W
W
Pharmakologisches Institut, Freiburg i.Br., Germany.
Schöffel
E
E
Szabo
B
B
Starke
K
K
D000200:Action Potentials; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000145:classification* / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003712:Dendrites / Q000378:metabolism*; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000378:metabolism* / Q000648:ultrastructure; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification* / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D017660:Autoreceptors; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D008376:Maprotiline; D015016:Yohimbine; C027299:hydroxymaprotilin; D000068438:Brimonidine Tartrate; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine