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A 2A and A 3 receptors mediate the adenosine‐induced relaxation in spontaneously active possum duodenum in vitro
Author(s) -
Woods C M,
Toouli J,
Saccone G T P
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705165
Subject(s) - adenosine , caffeine , medicine , purinergic receptor , endocrinology , contraction (grammar) , adenosine receptor , chemistry , adenosine a1 receptor , muscle contraction , receptor , biology , agonist
The aim of this study was to define the P1 purinergic receptors that regulate spontaneous or adenosine‐induced duodenal motor activity. Spontaneous contractile activity was recorded isometrically from possum longitudinal duodenal muscle strips. Adenosine (0.5 μ M –1 m M ) was administered noncumulatively and repeated after pretreatment with a P1 antagonist or tetrodotoxin (TTX, 1 μ M ), ( n =4–7). Antagonists used were: A 1 , 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 10 n M ); A 2A , 8‐(3‐chlorostyryl)caffeine (CSC, 10 μ M ); A 2B , 3‐isobutyl‐8‐pyrrolidinoxanthine (IPDX, 10 μ M ); A 3 , 9‐chloro‐2‐(2‐furanyl)‐5‐[(phenylacetyl) amino][1,2,4]‐triazolo(1,5‐c)quinazoline (MRS1220, 10 μ M ). Changes in activity are expressed as percentage of baseline. Statistical analysis utilised nonparametric tests. Adenosine ( n =34) induced a long‐lasting, concentration‐dependent decrease in activity by 55.6±3.2% area under curve (AUC), 47.3±4.0% contraction amplitude, 31.6±3.6% basal tension and 10.4±1.7% contraction frequency (all P <0.001). The adenosine‐induced decrease in contraction amplitude was blocked by CSC ( P <0.01) or inhibited by MRS1220 ( P <0.03) pretreatment, but not modified by TTX, DPCPX or IPDX pretreatment. Adenosine antagonists modified spontaneous contractile activity. Pretreatment with DPCPX or CSC increased basal tension, whereas IPDX or MRS1220 pretreatment decreased contractile activity. 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.British Journal of Pharmacology (2003) 138 , 1333–1339. doi: 10.1038/sj.bjp.0705165