A_2A and A₃ receptors mediate the adenosine‐induced relaxation in spontaneously active possum duodenum in vitro

Abstract

1 The aim of this study was to define the P1 purinergic receptors that regulate spontaneous or adenosine-induced duodenal motor activity. 2 Spontaneous contractile activity was recorded isometrically from possum longitudinal duodenal muscle strips. Adenosine (0.5 mm -1 mm) was administered noncumulatively and repeated after pretreatment with a P1 antagonist or tetrodotoxin (TTX, 1 mm), (n ¼ 4 -7). Antagonists used were: A 1 , 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nm); A 2A , 8-(3-chlorostyryl)caffeine (CSC, 10 mm); A 2B , 3-isobutyl-8-pyrrolidinoxanthine (IPDX, 10 mm); A 3 , 9-chloro-2-(2-furanyl)-5-[(phenylacetyl) amino][1,2,4]-triazolo(1,5-c)quinazoline (MRS1220, 10 mm). Changes in activity are expressed as percentage of baseline. Statistical analysis utilised nonparametric tests. 3 Adenosine (n ¼ 34) induced a long-lasting, concentration-dependent decrease in activity by 55.673.2% area under curve (AUC), 47.374.0% contraction amplitude, 31.673.6% basal tension and 10.471.7% contraction frequency (all Po0.001). The adenosine-induced decrease in contraction amplitude was blocked by CSC (Po0.01) or inhibited by MRS1220 (Po0.03) pretreatment, but not modified by TTX, DPCPX or IPDX pretreatment. 4 Adenosine antagonists modified spontaneous contractile activity. Pretreatment with DPCPX or CSC increased basal tension, whereas IPDX or MRS1220 pretreatment decreased contractile activity. 5 In conclusion, exogenous adenosine reduced duodenal longitudinal motor activity via A 2A and A 3 receptors. Our findings suggest that endogenous purines may modulate spontaneous duodenal motor activity.

A1 receptors mediate adenosine inhibitory effects in mouse ileum via activation of potassium channels

“…Thus, in mouse ileum we demonstrated the presence of A 1 relaxant receptors, as has been reported in rat duodenum and ileum (Nicholls et al 1996;Nicholls and Hourani 1997) and in mouse jejunum (De Man et al 2003a) and colon (Zizzo et al 2006). Indeed, although A 2 receptors mediate adenosineinduced muscular relaxation in a variety of intestinal preparations (Bailey and Hourani 1992;Nicholls et al 1996;Kadowaki et al 2000;Woods et al 2003;Zizzo et al 2006) we did not find evidence for the presence of functional A 2 inhibitory adenosine receptors in mouse ileum (present work) and in mouse proximal colon (Zizzo et al 2006), as well of A 3 receptors. In fact, neither DMPX nor MRS 1220, respectively A 2 and A 3 receptor antagonists, affected adenosine response indicating that it is unlikely a role for A 2 or A 3 receptors in the observed effect.…”

“…Adenosine receptors may be located postjunctionally (Serio et al 1990;Nicholls et al 1996;Kadowaki et al 2000;Woods et al 2003;De Man et al 2003a;Zizzo et al 2006) or on the enteric neurons regulating the neurotransmitter release (Tomaru et al 1995;Moneta et al 1997;Lee et al 2001;Storr et al 2002;De Man et al 2003b;Zizzo et al 2006).…”

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

“…Postjunctional P1 (A 1 and A 2 ) receptors mediate relaxation of rat and mouse duodenum longitudinal muscle [308,495,762]. Adenosine-induced relaxation of possum duodenum is mediated by A 3 , as well as A 2A receptors [711]. P1 (A l and/or A 2B ) receptors mediate contraction of rat ileal muscularis mucosae [508,509].…”

Purinergic receptors and synaptic transmission in enteric neurons

“…Adenosine applied to the intestine can influence intestinal functions by directly acting at adenosine receptors on smooth muscle [41][42][43] or by indirectly acting at adenosine receptors in the ENS to regulate neurotransmitter release [42,44,45]. This evidence suggests that adenosine receptors are located within the GI tract and, thus, that endogenous adenosine may play a physiological role.…”