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- Kull, B, et al.
(författare)
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Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors
- 1999
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Ingår i: Biochemical Pharmacology. - 0006-2952. ; 57:1, s. 65-75
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Tidskriftsartikel (refereegranskat)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.
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- Melander, Arne, et al.
(författare)
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Utilisation of antihyperglycaemic drugs in ten European countries: different developments and different levels.
- 2006
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 49:9, s. 2024-2029
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The aim of this study was to compare developments in the utilisation of antihyperglycaemic drugs (AHGDs) in ten European countries. Subhect and methods Data on the yearly utilisation of insulin and oral AHGDs were collected from public registers in Denmark, Finland, Norway, Sweden, Belgium, England, Germany, Italy, Portugal and Spain, and were expressed as defined daily doses per 1,000 inhabitants per day. Results Total AGHD utilisation increased everywhere, but at different rates and levels. Insulin utilisation doubled in England and Germany, but hardly changed in Belgium, Portugal or Italy. Sulfonylurea utilisation doubled in Spain, England and Denmark but was reduced in Germany and Sweden. Metformin utilisation increased greatly everywhere. There were two- to three-fold differences in AHGD utilisation even between neighbouring countries. In Finland, there were more users of both insulin (+120%) and oral AHGDs (+80%) than in Denmark, and the daily oral AHGD doses were higher. In Denmark and Sweden, AHGD utilisation was equal in subjects aged < 45 years, but in those >= 45 years of age, both insulin and oral AHGD utilisation were twice as high in Sweden. Conclusions/interpretation The ubiquitous increase in AHGD utilisation, particularly metformin, seems logical, considering the increasing prevalence of type 2 diabetes and the results of the UK Prospective Diabetes Study. However, the large differences even between neighbouring countries are more difficult to explain, and suggest different habits and attitudes in terms of screening and management of type 2 diabetes.
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