The role of adenosine A_2A and A₃ receptors on the differential modulation of norepinephrine and neuropeptide Y release from peripheral sympathetic nerve terminals

Abstract

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: 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 A 2A plus A 3 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 A 2A and A 3 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.

Impaired Function of Prejunctional Adenosine A1 Receptors Expressed by Perivascular Sympathetic Nerves in DOCA-Salt Hypertensive Rats

“…These data are consistent with our conclusion that A 1 Rs modulate NE release in the mesenteric circulation. This differs from the conclusion of Donoso et al (2006), who concluded that A 1 Rs do not couple to inhibition of NE release in the rat mesentery. Their conclusion is based in part on reverse-transcription polymerase chain reaction studies, which did not detect A 1 R transcripts in the mesentery.…”

“…This may be attributable to different potencies of adenosine analogs acting at A 1 Rs. In addition, adenosine may act the A 3 adenosine receptor, which also couples to inhibition of NE release (Donoso et al, 2006). Further studies are needed to clarify this issue.…”

“…(Todorov et al, 1997;Tabrizchi and Bedi, 2001;Westfall et al, 2002), modulates sympathetic neurotransmission in the mesenteric circulation (Illes et al, 1988;Ralevic, 1995;Diniz et al, 2004;Donoso et al, 2006), in the rat tail artery (Bucher et al, 1992;Diniz et al, 2004) in rat caudal arteries (Shinozuka et al, 1988), and in human forearm blood vessels (Rongen et al, 1996).…”

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

“…Effects of adenosine occur via activation of four membrane G-protein-coupled receptor subtypes, A 1 , A 2A , A 2B , and A 3 (1). This type of regulation has been previously described in rat caudal (2 -4), pulmonary (5), and mesenteric arteries (6,7).…”

Effect of Caffeine Chronically Consumed During Pregnancy on Adenosine A1 and A2A Receptors Signaling in Both Maternal and Fetal Heart from Wistar Rats

“…9,10,62 In vivo studies have suggested that A 2A and A 3 are responsible for this presynaptic effect. 63,64 Moreover, a significant increase in the adrenaline plus noradrenaline content in the heart has been reported in rats ingesting high doses of caffeine. 65 This increase would elicit a higher activation of b-adrenergic receptors and, in turn, would also contribute to the detected higher basal cAMP level.…”