The role of adenosine A2A and A3 receptors on the differential modulation of norepinephrine and neuropeptide Y release from peripheral sympathetic nerve terminals.

Autor: Donoso, M. Verónica, Aedo, Felipe, Huidobro-Toro, J. Pablo
Předmět:
Zdroj: Journal of Neurochemistry; Mar2006, Vol. 96 Issue 6, p1680-1695, 16p, 1 Diagram, 4 Charts, 5 Graphs
Abstrakt: The pre-synaptic sympathetic modulator role of adenosine was assessed by studying transmitter release following electrical depolarization of nerve endings from the rat mesenteric artery. Mesentery perfusion with exogenous adenosine exclusively inhibited the release of norepinephrine (NA) but did not affect the overflow of neuropeptide Y (NPY), establishing the basis for a differential pre-synaptic modulator mechanism. Several adenosine structural analogs mimicked adenosine's effect on NA release and their relative order of potency was: 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine hydrochloride = 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy- N-methyl-β-d-ribofuranuronamide = 5′-( N-ethylcarboxamido)adenosine >> adenosine > N6-cyclopentyladenosine. The use of selective receptor subtype antagonists confirmed the involvement of A2A and A3 adenosine receptors. The modulator role of adenosine is probably due to the activation of both receptors; co-application of 1 nm 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine hydrochloride plus 1 nm 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy- N-methyl-β-d-ribofuranuronamide caused additive reductions in NA released. Furthermore, while 1 nm of an A2A or A3 receptor antagonist only partially reduced the inhibitory action of adenosine, the combined co-application of the two antagonists fully blocked the adenosine-induced inhibition. Only the simultaneous blockade of the adenosine A2A plus A3 receptors with selective antagonists elicited a significant increase in NA overflow. H 89 reduced the release of both NA and NPY. We conclude that pre-synaptic A2A and A3 adenosine receptor activation modulates sympathetic co-transmission by exclusively inhibiting the release of NA without affecting immunoreactive (ir) -NPY and we suggest separate mechanisms for vesicular release modulation. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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