A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

• Published in: British journal of pharmacology 1999-02, Vol.126 (4), p.969-978
• Main Authors: Hernández, Medardo, Barahona, María Victoria, Bustamante, Salvador, García‐Sacristán, Albino, Orensanz, Luis M
• Format: Article
• Language: English
• Subjects: 8‐PT; Adenosine - pharmacology; adenosine receptors; Adenosine Triphosphate - pharmacology; Adenosine-5'-(N-ethylcarboxamide) - pharmacology; Adenosinic and purinergic receptors; Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; Dose-Response Relationship, Drug; DPCPX; Electric Stimulation; electrical field stimulation; Female; Fundamental and applied biological sciences. Psychology; Indomethacin - pharmacology; Male; Molecular and cellular biology; Muscle Relaxation - drug effects; NANC neurotransmission; Pig intravesical ureter; Receptors, Purinergic P1 - physiology; Swine; Synaptic Transmission - drug effects; Theophylline - analogs & derivatives; Theophylline - pharmacology; Ureter - drug effects; Ureter - innervation; Ureter - physiology; Vertebrates: urinary system; Xanthines - pharmacology; ZM 241385
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702386

The present study was designed to characterize the adenosine receptors involved in the relaxation of the pig intravesical ureter, and to investigate the action of adenosine on the non adrenergic non cholinergic (NANC) excitatory ureteral neurotransmission. In U46619 (10−7  M)‐contracted strips treated with the adenosine uptake inhibitor, nitrobenzylthioinosine (NBTI, 10−6  M), adenosine and related analogues induced relaxations with the following potency order: 5′‐N‐ethylcarboxamidoadenosine (NECA)=5′‐(N‐cyclopropyl)‐carboxamidoadenosine (CPCA)=2‐chloroadenosine (2‐CA)>adenosine>cyclopentyladenosine (CPA)=N6‐(3‐iodobenzyl)‐adenosine‐5′‐N‐methylcarboxamide (IB‐MECA)=2‐[p‐(carboxyethyl)‐phenylethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS21680). Epithelium removal or incubation with indomethacin (3×10−6  M) and L‐NG‐nitroarginine (L‐NOARG, 3×10−5  M), inhibitors of prostanoids and nitric oxide (NO) synthase, respectively, failed to modify the relaxations to adenosine. 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX, 10−8 M) and 4‐(2‐[7‐amino‐2‐(2‐furyl) [1,2,4]‐triazolo[2,3‐a][1,3,5]triazin‐5‐ylamino]ethyl)phenol (ZM 241385, 3×10−8  M and 10−7  M), A1 and A2A receptor selective antagonists, respectively, did not modify the relaxations to adenosine or NECA. 8‐phenyltheophylline (8‐PT, 10−5  M) and DPCPX (10−6  M), which block A1/A2‐receptors, reduced such relaxations. In strips treated with guanethidine (10−5  M), atropine (10−7  M), L‐NOARG (3×10−5  M) and indomethacin (3×10−6  M), both electrical field stimulation (EFS, 5 Hz) and exogenous ATP (10−4  M) induced contractions of preparations. 8‐PT (10−5  M) increased both contractions. DPCPX (10−8  M), NECA (10−4  M), CPCA, (10−4  M) and 2‐CA (10−4  M) did not alter the contractions to EFS. The present results suggest that adenosine relaxes the pig intravesical ureter, independently of prostanoids or NO, through activation of A2B‐receptors located in the smooth muscle. This relaxation may modulate the ureteral NANC excitatory neurotransmission through a postsynaptic mechanism. British Journal of Pharmacology (1999) 126, 969–978; doi:10.1038/sj.bjp.0702386