Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery.
1. We investigated the vascular effects of agmatine (decarboxylated arginine), an endogenous ligand for alpha 2-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 alpha 1- and alpha 2- 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 alpha 2-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 alpha 2-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.
Department of Physiology, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
C
C
González
S
S
Regunathan
D J
DJ
Reis
C
C
Estrada
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D002417:Cattle; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission; D013623:Tail / Q000098:blood supply
D000376:Agmatine; D009638:Norepinephrine