Article date: December 1988
By: Fritz Sladeczek, Bernard H. Schmidt, Robert N. Cory, Chakib Moatassim, Richard Alonso, Kenneth L. Kirk, Christopher J. Kirk, Bruno Rouot, Joël Bockaert in Volume 95, Issue 4, pages 1133-1140
The apparent Ki values of (−)noradrenaline (NA), (+)− and (−)‐adrenaline (Ad), phenylephrine and the mono‐fluorinated NAs (in position 2, 5 or 6) for α1‐adrenoceptors of intact BC3H1 cells labelled with [3H]‐prazosin were greatly dependent on the incubation temperature.
The EC50 values of these compounds for stimulation of the inositol phosphate (IP) accumulation at 37°C were intermediate between their apparent dissociation constants at 2°C (Ki2°) and at 37°C (Ki37°).
The fact that an irreversible blockade of 46% ± 6% (n = 3) of the [3H]‐prazosin binding sites by phenoxybenzamine reduced the maximal IP‐formation induced by NA by 57% ± 5% (n = 3) shows that there is a direct coupling between α1‐adrenoceptors and phospholipase C in BC3H1 cells.
The Ki37°s of all agonists tested were in the same range (0.1 to 1mm) and showed no simple correlation with their EC50 values.
The Ki2° values for all the agonist correlated linearly with their EC50 values but were about 20–100 times lower than the respective EC50 values (except for the partial agonist methoxamine). In order to explain this difference, we propose that the apparent high affinity in the cold could be due to an [3H]‐prazosin‐induced alteration of the active site of the α1‐adrenoceptor, increasing its apparent affinity for catecholamines.
The apparent Ki values of (−)noradrenaline (NA), (+)− and (−)‐adrenaline (Ad), phenylephrine and the mono‐fluorinated NAs (in position 2, 5 or 6) for α1‐adrenoceptors of intact BC3H1 cells labelled with [3H]‐prazosin were greatly dependent on the incubation temperature.
The EC50 values of these compounds for stimulation of the inositol phosphate (IP) accumulation at 37°C were intermediate between their apparent dissociation constants at 2°C (Ki2°) and at 37°C (Ki37°).
The fact that an irreversible blockade of 46% ± 6% (n = 3) of the [3H]‐prazosin binding sites by phenoxybenzamine reduced the maximal IP‐formation induced by NA by 57% ± 5% (n = 3) shows that there is a direct coupling between α1‐adrenoceptors and phospholipase C in BC3H1 cells.
The Ki37°s of all agonists tested were in the same range (0.1 to 1mm) and showed no simple correlation with their EC50 values.
The Ki2° values for all the agonist correlated linearly with their EC50 values but were about 20–100 times lower than the respective EC50 values (except for the partial agonist methoxamine). In order to explain this difference, we propose that the apparent high affinity in the cold could be due to an [3H]‐prazosin‐induced alteration of the active site of the α1‐adrenoceptor, increasing its apparent affinity for catecholamines.
DOI: 10.1111/j.1476-5381.1988.tb11748.x
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