Adenosine A_2A receptor‐mediated facilitation of noradrenaline release involves protein kinase C activation and attenuation of presynaptic inhibitory receptor‐mediated effects in the rat vas deferens

Abstract

In the epididymal portion of rat vas deferens, facilitation of noradrenaline release mediated by adenosine A2A receptors, but not that mediated by β2‐adrenoceptors or by direct activation of adenylyl cyclase, was attenuated by blockade of α2‐adrenoceptors and abolished by simultaneous blockade of α2‐adrenoceptors, adenosine A1 and P2Y receptors. The adenosine A2A receptor‐mediated facilitation was not changed by inhibitors of protein kinase A, protein kinase G or calmodulin kinase II but was prevented by inhibition of protein kinase C with chelerythrine or bisindolylmaleimide XI. Activation of protein kinase C with phorbol 12‐myristate 13‐acetate caused a facilitation of noradrenaline release that was abolished by bisindolylmaleimide XI and reduced by antagonists of α2‐adrenoceptors, adenosine A1 and P2Y receptors. Activation of adenosine A2A receptors attenuated the inhibition of noradrenaline release mediated by the presynaptic inhibitory receptors. This effect was mimicked by phorbol 12‐myristate 13‐acetate and prevented by bisindolylmaleimide XI. It is concluded that adenosine A2A receptors facilitate noradrenaline release by a mechanism that involves a protein kinase C‐mediated attenuation of effects mediated by presynaptic inhibitory receptors, namely α2‐adrenoceptors, adenosine A1 and P2Y receptors.

Determination of Adenosine Effects and Adenosine Receptors in Murine Corpus Cavernosum

“…Because adenosine has been shown to inhibit norepinephrine release from sympathetic nerve endings in a variety of in vitro models and because adenosine A1 receptors are thought to be involved in this inhibitory effect (De Mey et al, 1979;Illes et al, 1988;von Kugelgen et al, 1992;Grimm et al, 2001;Queiroz et al, 2003;Burnstock, 2006), we evaluated the effects of the adenosine A1 receptor agonist C8031 (10 Ϫ8 -10 Ϫ6 M; Klotz et al, 1989) on contractile responses induced by EFS in murine cavernosal strips (Fig. 6A).…”

“…Most commonly, the adenosine A1 receptor subtype negatively modulates norepinephrine release, whereas the A2 receptor subtypes enhance neurotransmitter release (von Kugelgen et al, 1992;Rongen et al, 1996;Burnstock, 2006). Considering that adenosine A1 prejunctional inhibitory receptors were described in a variety of tissues-canine saphenous vein (De Mey et al, 1979), rabbit mesenteric arteries (Illes et al, 1988), rat heart (Grimm et al, 2001), and rat vas deferens (Queiroz et al, 2003)-we decided to evaluate the effects of an adenosine A1 receptor agonist on contractile responses induced by EFS in murine cavernosal strips. The A1 agonist C8031 right-shifted the contractile responses to EFS, supporting a role for A1 receptors on the inhibitory effects induced by 5Ј-iodotubercidin, EHNA, and dipyridamole.…”

Effects of adenosine receptor antagonists in MPTP mouse model of Parkinson’s disease: mitochondrial DNA integrity

“…The cognitive effect of caffeine is mostly due to its ability to antagonize ADRsA 1 in the hippocampus and prefrontal cortex, the brain areas involved in cognition [47]. However, the ADRsA 2A are abundant in the striatum and other nuclei of the basal ganglia, where they are always co-localized with the dopaminergic D 2 receptors [48]. Queiroz et al [48] emphasized that ADRsA 1 maintain tonic homoeostatic adenosine functions, whereas ADRsA 2A mostly exert their fine-tuning modulation under some pathophysiological situations.…”

“…However, the ADRsA 2A are abundant in the striatum and other nuclei of the basal ganglia, where they are always co-localized with the dopaminergic D 2 receptors [48]. Queiroz et al [48] emphasized that ADRsA 1 maintain tonic homoeostatic adenosine functions, whereas ADRsA 2A mostly exert their fine-tuning modulation under some pathophysiological situations. Another possible explanation could be that ADRsA 1 activation depresses cholinergic transmission, which is important in learning and memory processes; thus, blockade of ADRsA 1 may indirectly stimulate cholinergic neurotransmission and thereby enhance cognition [48].…”

Nucleoside Triphosphate Diphosphohydrolase-1 Ectonucleotidase Is Required for Normal Vas Deferens Contraction and Male Fertility through Maintaining P2X1 Receptor Function

“…To our knowledge, the absence of the enzyme hydrolyzing AMP to generate adenosine from extracellular ATP and ADP, namely ecto-5Ј-nucleotidase, has no reported ejaculation defect, and, unlike ATP, adenosine has no proper contractile effect in vas deferens, and the net effect of adenosine on the contraction of vas deferens remains to be established. In vitro adenosine potentiates noradrenaline or ATP-dependent contraction through A1 receptor activation (40) and NA release through presynaptic A 2A receptor activation (41). On the other hand, adenosine reduces the contraction through A 2B receptors and inhibits NA release through presynaptic A 1 (42).…”