Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery

• Published in: British journal of pharmacology Vol. 119; no. 4; pp. 677 - 684
• Main Authors: González, C., Regunathan, S., Reis, D.J., Estrada, C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.1996; Nature Publishing
• Subjects: Agmatine - pharmacology; Animals; Arteries - drug effects; Arteries - innervation; Arteries - metabolism; Biological and medical sciences; Blood vessels and receptors; Cattle; Fundamental and applied biological sciences. Psychology; imidazoline (I‐) receptors; In Vitro Techniques; Male; noradrenergic transporter; Norepinephrine - metabolism; Presynaptic Terminals - drug effects; Rats; Rats, Sprague-Dawley; sympathetic nerves; Synaptic Transmission; Tail - blood supply; transmural nerve stimulation; Vertebrates: cardiovascular system; α2‐Adrenoceptors; α2-Adrenergic receptor; Rat; Rodentia; Catecholamine; Sympathetic nervous system; Muscle contraction; In vitro; Artery; Imidazoline receptor; Vertebrata; Vasomotricity; Mammalia; Amine; Endogenous; Animal; Blood vessel; Tail; Norepinephrine; Circulatory system; Mechanism of action; Agmatine; Neurotransmission
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15726.x

1 We investigated the vascular effects of agmatine (decarboxylated arginine), an endogenous ligand for α2‐adrenoceptors and non‐adrenoceptor imidazoline (I‐) receptors, present in endothelium, smooth muscle and plasma, using the rat tail artery as a model. 2 While by itself agmatine (10 nM‐1 mM) was without effect on isolated arterial rings, at the highest concentration used (1 mM) it slightly increased EC50 values for contractions elicited respectively by the α1‐ and α2‐adrenoceptor agonists methoxamine and clonidine. 3 Agmatine (0.03‐1 mM) produced a concentration‐dependent transient inhibition of the contractions induced by transmural nerve stimulation (TNS; 200 mA, 0.2 ms, 1 Hz, 10 s). This effect was abolished by the α2‐adrenoceptor antagonists, rawolscine and idazoxan. 4 In the presence of rawolscine or idazoxan, agmatine produced a concentration‐dependent delayed facilitation of TNS‐induced contractions, which was prevented by cocaine. 5 Neither inhibitory nor potentiating actions were produced by agmatine on contractions induced by noradrenaline (NA) administration. 6 Agmatine did not directly affect [3H]‐NA uptake in bovine cultured chromaffin cells. 7 Agmatine can regulate vascular function by two opposing actions at sympathetic nerve terminals, with different latencies: a transient inhibition of NA release mediated by prejunctional α2‐adrenoceptors and a cocaine‐sensitive delayed facilitation the mechanism of which is undetermined at present. 8 The results reveal the existence of a novel endogenous amine modulating NA release in the perivascular sympathetic terminals.