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Determination of α 1 ‐adrenoceptor subtype selectivity by [ 3 H]‐prazosin displacement studies in guinea‐pig cerebral cortex and rat spleen membranes
Author(s) -
Veenstra D.M.J.,
Buuren K.J.H.,
Nijkamp F.P.
Publication year - 1992
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.1476-5381.1992.tb14487.x
Subject(s) - prazosin , guinea pig , cerebral cortex , population , dissociation constant , membrane , chemistry , endocrinology , medicine , biology , biochemistry , receptor , antagonist , environmental health
1 [ 3 H]‐prazosin homogeneously labels α 1 ‐adrenoceptors in guinea‐pig cerebral cortex and rat spleen membranes with dissociation constants of 1.28 and 1.49 × 10 −10 m respectively. 2 Phentolamine and WB 4101 displacement studies show that guinea‐pig cerebral cortex contains 30% α 1A ‐ and 70% α 1B ‐adrenoceptor subtypes, whereas rat spleen contains a virtually homogeneous α 1B ‐adrenoceptor subtype population. The α 1 ‐adrenoceptor population of rat thoracic aorta is predominantly of the α 1A ‐adrenoceptor subtype, and in guinea‐pig thoracic aorta it is mainly of the α 1B ‐adrenoceptor subtype. 3 Half of the compounds displacing [ 3 H]‐prazosin bound to guinea‐pig cerebral cortex membranes display α 1A ‐adrenoceptor selectivity. Among these compounds, WB 4101 and methoxamine are most selective, displaying selectivity ratios of ∼38 and ∼26 respectively. 4 The affinity constants of the non‐selective compounds for the α 1 ‐adrenoceptors in guinea‐pig cerebral cortex membranes correlate well with the affinity constants obtained for α 1B ‐adrenoceptors in rat spleen membranes. The affinities of selective compounds for the α 1B ‐adrenoceptor subtype in guinea‐pig cerebral cortex correlate very well with their affinity for α 1B ‐adrenoceptor in the rat spleen homogenate. Both regression lines coincide with the line of identity. The affinity constants of selective compounds for the α 1A ‐adrenoceptors in guinea‐pig cerebral cortex only apparently correlate with the affinity for either the α 1B ‐adrenoceptors in guinea‐pig cerebral cortex or in the rat spleen. Regression analyses indicate a straight line relationship ( r 2 > 0.9) between p K α1A and p K α1B but the regression lines deviate from the line of identity.