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Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors

Kull, B; Arslan, G; Nilsson, C; Owman, Christer LU ; Lorenzen, A; Schwabe, U and Fredholm, B B (1999) In Biochemical Pharmacology 57(1). p.65-75
Abstract
To examine possible species differences in pharmacology, rat adenosine A2A receptors were studied in PC12 (pheochromocytoma) cells, and human receptors in Chinese hamster ovary (CHO) cells transfected with the cloned human A2A receptor cDNA. Using [3H]-5-amino-7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine ([3H]-SCH 58261) as radioligand, the estimated Bmax (maximal binding) was 538 and 2085 fmol/mg in CHO and PC12 cells, respectively. The Kd (dissociation constant) values for [3H]-SCH 58261 were 1.05 and 5.6 nM in the two cell types, respectively. The order of potency of antagonists and most agonists was the same in both cell types, but 2-phenylaminoadenosine and 2-chloroadenosine were relatively less potent... (More)
To examine possible species differences in pharmacology, rat adenosine A2A receptors were studied in PC12 (pheochromocytoma) cells, and human receptors in Chinese hamster ovary (CHO) cells transfected with the cloned human A2A receptor cDNA. Using [3H]-5-amino-7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine ([3H]-SCH 58261) as radioligand, the estimated Bmax (maximal binding) was 538 and 2085 fmol/mg in CHO and PC12 cells, respectively. The Kd (dissociation constant) values for [3H]-SCH 58261 were 1.05 and 5.6 nM in the two cell types, respectively. The order of potency of antagonists and most agonists was the same in both cell types, but 2-phenylaminoadenosine and 2-chloroadenosine were relatively less potent in PC12 cells than in CHO cells. In the functional assay, using cyclic AMP accumulation, all agonists tested were more potent in CHO than in PC12 cells, but this could not be readily explained by differences in adenylyl cyclase or in the expression of G proteins. As in the case of binding, the relative agonist potencies were similar for most compounds, but 2-phenylaminoadenosine and 2-chloroadenosine were more potent at human A2A receptors in CHO cells than predicted from the data obtained on rat A2A receptors in PC12 cells. Antagonists were approximately equipotent in the two cells. These results show that, despite only small differences in amino acid sequences and no difference in antagonist pharmacology, the relative order of potency of receptor agonists can differ between species homologues of the adenosine A2A receptor. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adenosine receptors, PC12 cells, species differences, cyclic AMP, cloned receptor, receptor binding
in
Biochemical Pharmacology
volume
57
issue
1
pages
65 - 75
publisher
Elsevier
external identifiers
  • pmid:9920286
  • scopus:0032901196
ISSN
0006-2952
DOI
10.1016/S0006-2952(98)00298-6
language
English
LU publication?
yes
id
2c401e9c-bd27-43a8-b6da-85bc85abb92d (old id 1115404)
date added to LUP
2008-07-08 09:09:33
date last changed
2017-01-01 04:54:04
@article{2c401e9c-bd27-43a8-b6da-85bc85abb92d,
  abstract     = {To examine possible species differences in pharmacology, rat adenosine A2A receptors were studied in PC12 (pheochromocytoma) cells, and human receptors in Chinese hamster ovary (CHO) cells transfected with the cloned human A2A receptor cDNA. Using [3H]-5-amino-7(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine ([3H]-SCH 58261) as radioligand, the estimated Bmax (maximal binding) was 538 and 2085 fmol/mg in CHO and PC12 cells, respectively. The Kd (dissociation constant) values for [3H]-SCH 58261 were 1.05 and 5.6 nM in the two cell types, respectively. The order of potency of antagonists and most agonists was the same in both cell types, but 2-phenylaminoadenosine and 2-chloroadenosine were relatively less potent in PC12 cells than in CHO cells. In the functional assay, using cyclic AMP accumulation, all agonists tested were more potent in CHO than in PC12 cells, but this could not be readily explained by differences in adenylyl cyclase or in the expression of G proteins. As in the case of binding, the relative agonist potencies were similar for most compounds, but 2-phenylaminoadenosine and 2-chloroadenosine were more potent at human A2A receptors in CHO cells than predicted from the data obtained on rat A2A receptors in PC12 cells. Antagonists were approximately equipotent in the two cells. These results show that, despite only small differences in amino acid sequences and no difference in antagonist pharmacology, the relative order of potency of receptor agonists can differ between species homologues of the adenosine A2A receptor.},
  author       = {Kull, B and Arslan, G and Nilsson, C and Owman, Christer and Lorenzen, A and Schwabe, U and Fredholm, B B},
  issn         = {0006-2952},
  keyword      = {adenosine receptors,PC12 cells,species differences,cyclic AMP,cloned receptor,receptor binding},
  language     = {eng},
  number       = {1},
  pages        = {65--75},
  publisher    = {Elsevier},
  series       = {Biochemical Pharmacology},
  title        = {Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors},
  url          = {http://dx.doi.org/10.1016/S0006-2952(98)00298-6},
  volume       = {57},
  year         = {1999},
}