[3H]RS79948-197 binding to human, rat, guinea pig and pig alpha2A-, alpha2B- and alpha2C-adrenoceptors. Comparison with MK912, RX821002, rauwolscine and yohimbine.
The Kd values of the recently introduced radioligand [3H]RS79948-197 ((8a R,12aS,13a-S)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-metho xy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]naphthyridine) were determined for the recombinant human and rat alpha2A-, alpha2B- and alpha2C- as well as guinea pig alpha2B- and alpha2c-adrenoceptors expressed in COS (CV-1 Origin, SV40) cells. In addition, the Kd values were also determined for [3H]RS79948-197 for the guinea pig spleen alpha2A-adrenoceptor and for pig alpha2A-, alpha2B- and alpha2C-adrenoceptors in membranes obtained from kidney and striatum. Available radioligands for alpha2-adrenoceptors, besides [3H]RS79948-197 are the tritiated forms of MK912 ((2S,12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octa hydro-2H-benzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2'-one), RX821002 (2-methoxy-idazoxan), rauwolscine and yohimbine. In the present article the binding constants of all these substances for the alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes in human, pig, rat and guinea pig are reviewed. In all species tested MK912 was alpha2C-selective, RX821002 showed a minor alpha2A-selectivity, whereas [3H]RS79948-197 was non-selective among the alpha2-adrenoceptor subtypes, showing high affinity for all three subtypes. Rauwolscine and yohimbine showed relatively low affinities for nmost of the alpha2-adrenoceptor subtypes investigated, the exception being rauwolscine having high affinity for the human and porcine alpha2C-adrenoceptors.
Uhlén
S
S
BioMedical Centre, Department of Pharmaceutical Biosciences, Uppsala University, Sweden. staffan.uhlen@farmbio.uu.se
Dambrova
M
M
Näsman
J
J
Schiöth
H B
HB
Gu
Y
Y
Wikberg-Matsson
A
A
Wikberg
J E
JE
D018663:Adrenergic Agents / Q000378:metabolism*; D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism*; D009287:Naphthyridines / Q000378:metabolism*; D011807:Quinolizines / Q000378:metabolism; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013552:Swine; D015016:Yohimbine / Q000378:metabolism
C547768:ADRA2A protein, human; C547771:ADRA2B protein, human; C547774:ADRA2C protein, human; C547770:Adra2a protein, rat; C547773:Adra2b protein, rat; C547776:Adra2c protein, rat; D018663:Adrenergic Agents; D007546:Isoquinolines; D009287:Naphthyridines; D011807:Quinolizines; C104875:RS 79948-197; D018341:Receptors, Adrenergic, alpha-2; C054290:L 657743; D015016:Yohimbine; C058525:2-methoxyidazoxan; D019329:Idazoxan