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A STUDY OF α 1 ‐ADRENOCEPTORS IN RAT RENAL CORTEX: COMPARISON OF [ 3 H]‐PRAZOSIN BINDING WITH THE α 1 ‐ADRENOCEPTOR MODULATING GLUCONEOGENESIS UNDER PHYSIOLOGICAL CONDITIONS
Author(s) -
McPHERSON G.A.,
SUMMERS R.J.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb09284.x
Subject(s) - prazosin , oxymetazoline , phentolamine , phenylephrine , chemistry , gluconeogenesis , endocrinology , medicine , agonist , receptor , antagonist , biology , biochemistry , metabolism , blood pressure
1 A comparison has been made of the α 1 ‐adrenoceptor controlling gluconeogenesis in tubules from rat renal cortex and [ 3 H]‐prazosin binding in membranes prepared from the same tissue under physiological conditions. 2 In renal tubules the α‐adrenoceptor agonists, oxymetazoline, (−)‐noradrenaline, (−)‐α‐methylnoradrenaline and (−)‐phenylephrine, stimulated gluconeogenesis from pyruvate. Oxymetazoline was the most potent agonist (EC 50 15.7 n m ) but produced only 61% of the maximum response elicited by (−)‐noradrenaline. 3 The α‐adrenoceptor antagonists, BE2254, prazosin, indoramin and phentolamine inhibited (−)‐noradrenaline‐mediated increases in gluconeogenesis. The α 1 ‐adrenoceptor selective compounds, BE2254 and prazosin, were the most effective antagonists with K B values of 0.74 and 1.47 n m respectively. 4 [ 3 H]‐prazosin binding to membranes prepared from rat renal cortex in physiological saline at 37°C was best described by a two site model. High affinity, but not low affinity sites had characteristics consistent with α‐adrenoceptors. 5 High affinity [ 3 H]‐prazosin binding could be completely displaced by the α‐adrenoceptor agonists, oxymetazoline, (−)‐noradrenaline, (−)‐phenylephrine, and (−)‐α‐methylnoradrenaline. Slope factors for the displacement curves were all significantly less than unity. The concentrations of agonists required to displace [ 3 H]‐prazosin binding were markedly higher than those required to stimulate gluconeogenesis. 6 High‐affinity [ 3 H]‐prazosin binding was also displaced by the α‐adrenoceptor antagonists, prazosin, BE2254, phentolamine and indoramin. Slope factors for the displacement curves were close to unity. K i values calculated from the binding experiments were very similar to K B values obtained in the gluconeogenesis studies. These results suggest that in rat renal cortex the α 1 ‐adrenoceptor labelled by [ 3 H]‐prazosin is probably that which stimulates gluconeogenesis.