Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical usage of amphotericin B in treating systemic fungal infections is limited by its nephrotoxicity, which is caused by reductions in renal blood flow and alterations in renal tubular function. Aminophylline, an adenosine receptor antagonist, attenuates amphotericin B-induced reductions in renal blood flow in both dogs and rats, which suggests that endogenous adenosine may participate in this response. However, aminophylline per se is a vasodilator and also changes intracellular levels of cyclic nucleotides and calcium. In this study, we re-examined the hypothesis that adenosine participates in amphotericin B-induced renal vasoconstriction by employing a novel adenosine receptor antagonist, 1,3-dipropyl-8-(p-sulfophenyl)xanthine (DPSPX). This antagonist because of its negative charge at physiological pH, has limited access to the intracellular space. In a group of male Sprague-Dawley rats, an extracorporeal shunt was established between the carotid artery and left renal artery, via an aortic pouch, such that flow through the shunt was equivalent to renal blood flow. Also, a catheter was inserted into the left ureter for collection of urine and measurement of creatinine and electrolyte excretion. Amphotericin B-induced changes in renal blood flow and renal excretory function were measured in both control rats and rats pretreated with DPSPX at a dosage that abolishes the renovascular effects of exogenous adenosine in this model. In both control rats and rats pretreated with DPSPX, amphotericin B caused a marked decrease in renal blood flow, creatinine excretion, and potassium excretion; however, these effects of amphotericin B were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of an adenosine receptor antagonist on acute amphotericin B nephrotoxicity. 234 Aug 62

1. 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. 2. 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-ethylcarboxamidoaden os ine (CGS21680). 3. Epithelium removal or incubation with indomethacin (3 x 10(-6) M) and L-N(G)-nitroarginine (L-NOARG, 3 x 10(-5) M), inhibitors of prostanoids and nitric oxide (NO) synthase, respectively, failed to modify the relaxations to adenosine. 4. 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 x 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. 5. In strips treated with guanethidine (10(-5) M), atropine (10(-7) M), L-NOARG (3 x 10(-5) M) and indomethacin (3 x 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. 6. 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.
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PMID:A2B adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission. 1019 77