title: Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptors.
abstract: It has been suggested that agmatine (decarboxylated arginine) is an endogenous clonidine-displacing substance (CDS) which recognizes alpha 2-adrenoceptor and non-adrenoceptor, imidazoline binding sites. We have examined the effect of agmatine at alpha 2-adrenoceptor binding sites and pre- and postjunctional alpha 2-adrenoceptors. Agmatine produced a concentration-dependent inhibition of 1 nmol/l 3H-clonidine binding to both rat (pKi-5.10 +/- 0.05) and bovine (pKi-4.77 +/- 0.38) cerebral cortex membranes. However, agmatine (0.1-100 microM) failed to activate pre-junctional alpha 2-adrenoceptors regulating transmitter release in the guinea-pig isolated ileum and rat isolated vas deferens, nor did it activate postjunctional alpha 2-adrenoceptors of the porcine isolated palmar lateral vein which mediate contraction or inhibition of forskolin-stimulated cyclic AMP formation. High concentrations of agmatine (10-30-fold the pKi at alpha 2-adrenoceptor binding sites) failed to influence alpha 2-adrenoceptor activation by either clonidine or UK-14304 (5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate) in any of the peripheral preparations examined. Moreover, even in a preparation where an interaction with alpha 2-adrenoceptor binding sites on cell membranes can be demonstrated, the rat cerebral cortex, agmatine failed to inhibit forskolin-stimulated cyclic AMP in the intact tissue or affect the inhibition produced by the selective alpha 2-adrenoceptor agonist UK-14304. Agmatine was also devoid of agonist activity in two preparations, the rat isolated thoracic aorta and the rat isolated gastric fundus, in which CDS has been reported to produce non-adrenoceptor effects. Thus, we have confirmed that agmatine recognizes alpha 2-adrenoceptor binding sites and, therefore, is a CDS.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, UK.
authors.forename: D
authors.initials: D
authors.lastname: Pinthong
authors.forename: I K
authors.initials: IK
authors.lastname: Wright
authors.forename: C
authors.initials: C
authors.lastname: Hanmer
authors.forename: P
authors.initials: P
authors.lastname: Millns
authors.forename: R
authors.initials: R
authors.lastname: Mason
authors.forename: D A
authors.initials: DA
authors.lastname: Kendall
authors.forename: V G
authors.initials: VG
authors.lastname: Wilson
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D000376:Agmatine; D000242:Cyclic AMP; D003000:Clonidine