Characterization of the alpha-2C adrenergic receptor subtype in the opossum kidney and in the OK cell line.
The alpha-2 adrenergic receptors have been subdivided into two pharmacological subtypes known as alpha-2A and alpha-2B. The OK cell, a cell line derived from an opossum kidney, expresses an alpha-2 adrenergic receptor which has pharmacological characteristics different from both the alpha-2A and alpha-2B subtypes, and thus may be a third subtype. To test this hypothesis, we compared the affinities (Ki values from radioligand binding) of 49 drugs in the OK cell with their affinity for the alpha-2A (HT-29 cells) and alpha-2B (neonatal rat lung) adrenergic receptor subtypes. Eight drugs (spiroxarine, prazosin, WY 27127, L-657,743, ARC 239, akuammigine, rauwolscine and oxymetazoline) were identified whose Ki differed by 10-fold or more between the OK cells and HT29 cells. Five drugs (BAM 1303, raubasine, WB 4101, akuammigine and rauwolscine) differentiated, by at least 10-fold, between OK cells and neonatal rat lung. Correlations of pKi values between the OK cell and tissues or cell lines expressing either the alpha-2A or alpha-2B subtypes were poor, confirming that the OK cell receptor could not be classified as either alpha-2A or alpha-2B. In contradistinction, there was a good correlation between pKi values for the OK cell line and opossum kidney showing that they express the same subtype. In addition, ratios of subtype-selective drug Ki values were similar for the OK cell and opossum kidney, but different from other tissues or cell lines expressing either the alpha-2A or alpha-2B subtypes. We conclude that the OK cell line and opossum kidney express a novel subtype of alpha-2 adrenergic receptor which we term the alpha-2C subtype.
Blaxall
H S
HS
Department of Pharmacology, University of Nebraska Medical Center, Omaha.
Murphy
T J
TJ
Baker
J C
JC
Ray
C
C
Bylund
D B
DB
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009893:Opossums; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D011942:Receptors, Adrenergic, alpha