No evidence for activation of alpha(2)-adrenoceptors by methanolic extracts of bovine brain and lung containing clonidine-displacing substance.
Methanolic extracts of bovine brain and lung are capable of displacing [(3)H]-clonidine from alpha(2)-adrenoceptor binding sites, indicating the presence of a clonidine-displacing substance (CDS). We have examined alpha(2)-adrenergic responses and the extracts in three models: [(3)H]-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 alpha(2)-adrenoceptor agonist, 5-bromo-6-2-imidazolin-2-ylamino]-quinoxaline bitartrate (UK-14304) inhibited forskolin-stimulated [(3)H]-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 alpha(2)-adrenoceptor antagonists, idazoxan or rauwolscine. Brain CDS (5 units/mL) reduced forskolin-stimulated [(3)H]-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 microM 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 microM 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 alpha(2)-adrenoceptors.
Pinthong
D
D
School of Biomedical Sciences, The Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Kendall
D A
DA
Maclennan
S J
SJ
Eglen
R M
RM
Wilson
V G
VG
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D000068438:Brimonidine Tartrate; D002417:Cattle; D003000:Clonidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000737:chemistry*; D008297:Male; D000432:Methanol / Q000737:chemistry; D011810:Quinoxalines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013552:Swine; D014020:Tissue Extracts / Q000737:chemistry*; D014649:Vas Deferens / Q000378:metabolism; D014680:Veins / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014020:Tissue Extracts; D005576:Colforsin; D000068438:Brimonidine Tartrate; C055140:clonidine-displacing substance; D000242:Cyclic AMP; D003000:Clonidine; D000432:Methanol