Characterization of a new radioiodinated probe for the alpha2C adrenoceptor in the mouse brain.
[125I]17alpha-hydroxy-20alpha-yohimban-16beta-(N-4-p6 hydroxyphenethyl)carboxamide or [125I]rauwolscine-OHPC, a new radioiodinated probe derived from rauwolscine was synthesized and its binding characteristics investigated on sections of the mouse caudate putamen. [125I]rauwolscine-OHPC binding was saturable and revealed interaction with a single class of binding sites (KD= 0.171 nM, Bmax = 3082 pCi/mg of tissue). The kinetically derived affinity was in close agreement with the affinity evaluated by saturation experiments: k(-1)/k(+1)(0.0403 min(-1)/114 10(6) M(-1) min(-1))=0.35 nM. Competition studies revealed interaction with one single class of binding sites for each of the twelve compounds tested. The rank of potency suggested an interaction with alpha2 adrenoceptors (atipamezole > or = RX 821002 > yohimbine > (-)epinephrine). Moreover, the good affinity of [125I] rauwolscine-OHPC binding sites for spiroxatrine, yohimbine, WB 4101, the relatively good affinity for prazosin (Ki =37.4 nM) and the affinity ratio prazosin/oxymetazoline (37.4/43.4=0.86) were consistent with an alpha2C selective labelling of [125I]rauwolscine-OHPC. The distribution of [125I]rauwolscine-OHPC binding sites in mouse brain was characterized by autoradiography. The density of binding sites was high in the islands of Calleja, accumbens nucleus, caudate putamen and olfactory tubercles, moderate in the hippocampus, amygdala and anterodorsal nucleus of the thalamus. These findings demonstrated that [125I]rauwolscine-OHPC is a useful radioiodinated probe to label alpha2C adrenoceptors in mouse brain.
Dossin
O
O
Institut de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, Toulouse, France.
Moulédous
L
L
Baudry
X
X
Tafani
J A
JA
Mazarguil
H
H
Zajac
J M
JM
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009928:Organ Specificity; D010109:Oxymetazoline / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011699:Putamen / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis / Q000378:metabolism*; D015016:Yohimbine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
C547775:Adra2c protein, mouse; D007457:Iodine Radioisotopes; D018341:Receptors, Adrenergic, alpha-2; C404787:iodinated rauwolscine-OHPC; C404788:rauwolscine-OHPC; D015016:Yohimbine; D010109:Oxymetazoline; D011224:Prazosin; D004837:Epinephrine