Determination of alpha 1-adrenoceptor subtype selectivity by [3H]-prazosin displacement studies in guinea-pig cerebral cortex and rat spleen membranes
| Autor: | K.J.H. van Buuren, D. M. J. Veenstra, Frans P. Nijkamp |
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| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Population Guinea Pigs Alpha (ethology) Biology Guinea pig Dioxanes Radioligand Assay Internal medicine medicine Prazosin Animals Rats Wistar education Phentolamine Adrenergic alpha-Antagonists Pharmacology Cerebral Cortex education.field_of_study Binding Sites Biological membrane Receptors Adrenergic alpha Rats Dissociation constant Endocrinology medicine.anatomical_structure Membrane Cerebral cortex Adrenergic alpha-Agonists Spleen medicine.drug Research Article |
| Zdroj: | British journal of pharmacology. 107(1) |
| ISSN: | 0007-1188 |
| Popis: | 1. [3H]-prazosin homogeneously labels alpha 1-adrenoceptors in guinea-pig cerebral cortex and rat spleen membranes with dissociation constants of 1.28 and 1.49 x 10(-10) M respectively. 2. Phentolamine and WB 4101 displacement studies show that guinea-pig cerebral cortex contains 30% alpha 1A- and 70% alpha 1B-adrenoceptor subtypes, whereas rat spleen contains a virtually homogeneous alpha 1B-adrenoceptor subtype population. The alpha 1-adrenoceptor population of rat thoracic aorta is predominantly of the alpha 1A-adrenoceptor subtype, and in guinea-pig thoracic aorta it is mainly of the alpha 1B-adrenoceptor subtype. 3. Half of the compounds displacing [3H]-prazosin bound to guinea-pig cerebral cortex membranes display alpha 1A-adrenoceptor selectivity. Among these compounds, WB 4101 and methoxamine are most selective, displaying selectivity ratios of approximately 38 and approximately 26 respectively. 4. The affinity constants of the non-selective compounds for the alpha 1-adrenoceptor in guinea-pig cerebral cortex membranes correlate well with the affinity constants obtained for alpha 1B-adrenoceptors in rat spleen membranes. The affinities of selective compounds for the alpha 1B-adrenoceptor subtype in guinea-pig cerebral cortex correlate very well with their affinity for alpha 1B-adrenoceptor in the rat spleen homogenate. Both regression lines coincide with the line of identity. The affinity constants of selective compounds for the alpha 1A-adrenoceptors in guinea-pig cerebral cortex only apparently correlate with the affinity for either the alpha 1B-adrenoceptors in guinea-pig cerebral cortex or in the rat spleen. Regression analyses indicate a straight line relationship (r20.9) between pKEA and Pk1B but the regression lines deviate from the line of identity. |
| Databáze: | OpenAIRE |
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