Alpha2-adrenoceptors modulating neuronal serotonin release: a study in alpha2-adrenoceptor subtype-deficient mice.
1. The release-inhibiting alpha2-adrenoceptors of cerebral serotoninergic axons were studied in mice. Slices of the hippocampus or the occipito-parietal cortex from NMRI mice, from mice lacking the alpha2A/D-, the alpha2B-, the alpha2C- or both the alpha2A/D- and the alpha2C-adrenoceptor, and from mice sharing the genetic background of the receptor-deficient animals (WT) were preincubated with [3H]-serotonin and then superfused and stimulated electrically, in most experiments by trains of 8 pulses at 100 Hz. 2. The concentration-response curves of the alpha2-adrenoceptor agonist medetomidine were virtually identical in hippocampal slices from NMRI and WT mice, with maximally 70% inhibition and an EC50 of about 2 nM. In hippocampal slices from NMRI mice, phentolamine and rauwolscine were equipotent antagonists against medetomidine. 3. The effect of medetomidine was greatly reduced, with maximally 20% inhibition, in hippocampal slices from alpha2A/D-adrenoceptor-deficient mice; was slightly reduced, with maximally 59% inhibition, in hippocampal slices from alpha2C-adrenoceptor-deficient mice; was not changed in hippocampal slices from alpha2B-adrenoceptor-deficient mice; and was abolished in hippocampal slices from mice lacking both the alpha2A/D- and the alpha2C-adrenoceptor. 3. Similar results were obtained in: (i) occipito-parietal slices from NMRI and alpha2A/D-adrenoceptor-deficient mice and (ii) hippocampal slices that were preincubated with [3H]-serotonin in the presence of oxaprotiline to rule out cross-labelling of noradrenergic axons. 5. The serotoninergic axons of the mouse brain possess both alpha2A/D-heteroreceptors, which predominate, and alpha2C-heteroreceptors but lack alpha2B-adrenoceptors. The situation resembles the coexistence of alpha2A/D- and alpha2C-autoreceptors but lack of alpha2B-autoreceptors at the noradrenergic axons of mice.
Scheibner
J
J
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Hermann-Herder-Strasse 5, D-79104 Freiburg i. Br., Germany.
Trendelenburg
A U
AU
Hein
L
L
Starke
K
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D020926:Medetomidine / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009778:Occipital Lobe / Q000378:metabolism; D010296:Parietal Lobe / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D012701:Serotonin; D020926:Medetomidine; D010646:Phentolamine