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 α2-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 by 1 mM 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 mM 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.