Abstract
It has been suggested that agmatine (decarboxylated arginine) is an endogenous clonidine-displacing substance (CDS) which recognizes α2-adrenoceptor and non-adrenoceptor, imidazoline binding sites. We have examined the effect of agmatine at α2-adrenoceptor binding sites and pre- and postjunctional α2-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 μM) failed to activate pre-junctional α2-adrenoceptors regulating transmitter release in the guinea-pig isolated ileum and rat isolated vas deferens, nor did it activate post-junctional α2-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 α2-adrenoceptor binding sites) failed to influence α2-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 α2-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 α2-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 α2-adrenoceptor binding sites and, therefore, is a CDS. However, since agmatine is devoid of pharmacological activity at either peripheral or central α2-adrenoceptors it can not account for earlier reports suggesting that brain-derived CDS can activate α2-adrenoceptors.
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Pinthong, D., Wright, I.K., Hammer, C. et al. Agmatine recognizes α2-adrenoceptor binding sites but neither activates nor inhibits α2-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 351, 10–16 (1995). https://doi.org/10.1007/BF00169058
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DOI: https://doi.org/10.1007/BF00169058