No Evidence for Activation of α₂-Adrenoceptors by Methanolic Extracts of Bovine Brain and Lung Containing Clonidine-Displacing Substance

Methanolic extracts of bovine brain and lung are capable of displacing [³H]-clonidine from α₂-adrenoceptor binding sites, indicating the presence of a clonidine-displacing substance (CDS). We have examined α₂-adrenergic responses and the extracts in three models: [³H]-cyclic AMP accumulation in miniprisms of guinea pig cerebral cortex, isometric tension measurements of isolated segments of the rat vas deferens, and porcine palmar lateral vein. The selective α ₂-adrenoceptor agonist, 5-bromo-6-2-imidazolin-2-ylamino] -quinoxaline bitartrate (UK-14304) inhibited forskolin-stimulated [ ³H]-cyclic AMP accumulation in the cerebral cortex and elicited contractions of the porcine isolated palmar lateral vein. Clonidine (0.1-30 nM) inhibited neurogenic contractions of the rat vas deferens. Responses to both agonists were inhibited by the α₂-adrenoceptor antagonists, idazoxan or rauwolscine. Brain CDS (5 units/mL) reduced forskolin-stimulated [³H]-cyclic AMP accumulation in the guinea pig cerebral cortex, whereas lung CDS (1 unit/mL) increased the accumulation of the cyclic nucleotide. Neither response to the extracts was inhibited hy 1 μM idazoxan. Low concentrations of both extracts (0.05 unit/mL) reduced electrically evoked contractions of the rat vas deferens by approximately 20%, but higher concentrations enhanced neurogenic contractions by approximately 50%. Again, the effect of the brain extract was not altered by 1 μM idazoxan. Lung CDS (0.02-1 unit/mL) induced contractions of the porcine palmar lateral vein that were also insensitive to rauwolscine. The results suggest that brain and lung CDS do not activate either central or peripheral α₂- adrenoceptors.