Species orthologs of the alpha-2A adrenergic receptor: the pharmacological properties of the bovine and rat receptors differ from the human and porcine receptors.
Four pharmacological subtypes of the alpha-2 adrenergic receptor have been identified; however, only three subtypes exist in any given species. Although the alpha-2A adrenergic receptor, as defined by the human platelet, and the alpha-2D receptor, as defined in the bovine pineal, have very different pharmacological characteristics, they are more similar to each other than either is to the alpha-2B or alpha-2C subtype. The human alpha-2-C10 clone (alpha-2A) and the rat RG20 clone have an 89% identity in their predicted amino acid sequence and are considered to be species orthologs. Although the expressed RG20 clone appears to have alpha-2D pharmacology, a careful comparison of its pharmacological characteristics with the bovine pineal has not been reported previously. Based on the pKi values of a panel of 13 alpha-2 adrenergic agents that have been used previously to compare the alpha-2A, alpha-2B and alpha-2C subtypes, the pharmacological characteristics of the bovine pineal alpha-2D receptor appear to be very similar to the rat RG20 clone (correlation coefficient, r, of 0.93). The porcine ortholog of the human alpha-2-C10 receptor has pharmacological characteristics identical to the human alpha-2A receptor (r = 0.99). Because of its higher affinity for the alpha-2D receptor, [3H]RX821002 is a better radioligand than [3H]rauwolscine for studying this receptor subtype.
Department of Pharmacology, University of Nebraska Medical Center, Omaha.
M F
MF
O'Rourke
L J
LJ
Iversen
J W
JW
Lomasney
D B
DB
Bylund
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002460:Cell Line; D004146:Dioxanes / Q000378:metabolism; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000145:classification* / Q000378:metabolism; D013045:Species Specificity; D013552:Swine; D015016:Yohimbine / Q000378:metabolism
D004146:Dioxanes; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C058525:2-methoxyidazoxan; D019329:Idazoxan