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 local motor response to bradykinin and the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated in the guinea-pig isolated renal pelvis and ureter in relation to possible activation of capsaicin-sensitive primary afferent nerves and release of sensory neuropeptides. Both bradykinin (1 nM-10 microM) and FMLP (10 nM-10 microM) produced a concentration-dependent positive inotropic effect in the isolated renal pelvis which was unaffected by in vitro capsaicin desensitization. The response to bradykinin was antagonized by HOE 140, a bradykinin receptor antagonist, while it was unaffected by MEN 10,376, a tachykinin receptor antagonist, hCGRP(8-37) a calcitonin gene-related peptide (CGRP) receptor antagonist and N-t-BOC-Phe-DLeu-Phe-DLeu-Phe (BPLPLP), an FMLP antagonist. The response to FMLP was blocked by BPLPLP while it was unaffected by HOE 140, MEN 10,376 or hCGRP(8-37). Indomethacin (10 microM) enhanced the response to both bradykinin and FMLP. Bradykinin transiently activated rhythmic contractions in the isolated ureter. The response to bradykinin was blocked by HOE 140 and was unaffected by in vitro capsaicin desensitization, indomethacin, MEN 10,376 or BPLPLP. FMLP had no motor effect on the resting ureter but when rhythmic background contractions were evoked by the addition of 100 nM endothelin 1, it produced a transient suppression of ureteral motility. This inhibitory effect was unchanged by in vitro capsaicin desensitization or HOE 140 while it was abolished by indomethacin or BPLPLP pretreatment. Both bradykinin and FMLP evoked the release of CGRP-like immunoreactivity in the renal pelvis. The effect of bradykinin but not that of FMLP was abolished by indomethacin. By contrast neither bradykinin nor FMLP did evoke a significant CGRP-LI release in the ureter. It is concluded that bradykinin and FMLP affect pyeloureteral motility through specific and independent pathways. The local motor responses produced by these chemical stimulants are independent from the release of sensory neuropeptides from capsaicin-sensitive primary afferent neurons. Direct neurochemical evidence was obtained for activation of capsaicin-sensitive primary afferents in the renal pelvis: such a mechanism could be involved in the genesis of ureteral pain whenever bradykinin or FMLP come into contact with sensory nerves in the pyeloureteral wall.
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PMID:Local motor responses to bradykinin and bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) in the guinea-pig isolated renal pelvis and ureter. 133 50

A bolus injection of a very low dose (100 ng) of endotoxin into an isolated perfused hydronephrotic (3 day unilateral ureter obstructed) kidney resulted in the appearance of substances in the venous effluent, which caused a biphasic chronic contraction of intestinal and vascular smooth muscle bioassay strips. Indomethacin pretreatment blocked the effect. The contralateral (unobstructed) rabbit kidney, postobstructed hydronephrotic rabbit kidney (i.e., release of ureter obstruction for 3-10 days) and the hydronephrotic cat kidney did not respond to endotoxin. Histological examination demonstrated that the hydronephrotic rabbit kidney contains mononuclear cells, whereas the unobstructed contralateral rabbit kidney as well as the postobstructed rabbit hydronephrotic kidney and the hydronephrotic cat kidney have considerably fewer mononuclear cells. The responsiveness of the hydronephrotic rabbit kidney to endotoxin is dependent on ex vivo perfusion time and is suppressed by inhibition of protein synthesis with cycloheximide. These data suggest that ureter obstruction in the rabbit stimulates the infiltration of macrophages which are sensitive to endotoxin and which participate in the exaggerated prostaglandin production.
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PMID:Endotoxin induces chronic prostaglandin and thromboxane synthesis from ureter-obstructed kidneys: role of inflammatory cells. 640 96

The ANRL was derived from the renal venous effluent as the kidney exerted its nonexcretory antihypertensive function. This was made possible by three developments: (1) improvement in the extraction of ANRL from fresh renal medulla; (2) the fact that purified ANRL caused an acute vasodepressor effect (acted as a vasodilator); and (3) experience with unclipping the one-kidney, one-clip hypertensive rat. Unclipping after an anastomosis between the ureter and the vena cava caused the MAP to return to normal levels in an average of 20 hr. At an average of 5 hr, when the MAP had dropped an average of 34 mm Hg (from approximately 190), an exchange infusion was started and blood was collected from the renal vein. The plasma was separated, lyophilized, and extracted for total lipids. The lipids were subjected to two TLC procedures and tested for vasodepressor activity. Renal venous effluent, under those conditions, yielded a considerable amount of vasodepressor lipid that was similar to that derived from fresh renal medulla. Controls (normal, nephrectomized, and hypertensive animals) yielded little or no such lipid. Indomethacin did not interfere with the derivation of the vasodepressor lipid. As the MAP was lowered and the ANRL-like lipid appeared in the renal venous blood, the RICs degranulated. The RICs appear to be the source of the antihypertensive lipid.
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PMID:Derivation of antihypertensive neutral renomedullary lipid from renal venous effluent. 679 54

1. The effects of the (S)- and (R)-enantiomers of the cyclo-oxygenase (COX) inhibitor, ketoprofen, have been investigated on the spontaneous activity of the guinea-pig isolated renal pelvis and on electrical field stimulation-(EFS) induced contractions of the guinea-pig ureter in comparison with the effects of the achiral COX inhibitor, indomethacin. 2. (S)-ketoprofen (0.1-100 microM) produced a concentration- and time-dependent inhibition of the spontaneous myogenic activity of the renal pelvis. The maximal inhibitory effect (% inhibition of motility index) averaged 29, 42, 47 and 56% inhibition of control values at 0.1, 1, 10 and 100 microM. The (R)-enantiomer was ineffective up to 10 microM. 3. Indomethacin (0.1-100 microM) likewise produced a concentration- and time-dependent inhibition of spontaneous motility of the isolated renal pelvis: its maximal inhibitory effect was larger than that produced by (S)-ketoprofen and averaged 21, 40, 69 and 95% inhibition of motility index at 0.1, 1, 10 and 100 microM respectively. In the presence of a maximally effective (100 microM) concentration of (S)-ketoprofen, 100 microM indomethacin produced > 90% inhibition of residual motility. 4. In the guinea-pig isolated ureter, phasic contractions were induced by EFS (5 ms pulse width, 60 V): (S)-ketoprofen (100-500 microM) had no effect on the EFS-evoked contractions. Indomethacin (100-500 microM) produced a concentration-dependent inhibition and/or suppression of the EFS-evoked contractions. When contraction of the ureter was evoked by 80 mM KCl, indomethacin produced about 30 and 80% inhibition at 100 and 300 microM, respectively, while (S)-ketoprofen (300 microM) was ineffective. 5. The effect of (S)-ketoprofen or indomethacin (10 microM each) on the propagation of myogenic impulses along the ureter was determined by use of a three chamber organ bath. The renal end of the ureter was electrically stimulated while recording the mechanical activity of the renal and bladder ends of the ureter: addition of either (S)-ketoprofen or indomethacin (10 microM) did not effect propagation of impulses from the renal to the bladder end of the ureter, while nifedipine (10 microM) promptly blocked the propagated contractions. 6. In sucrose gap experiments, (S)-ketoprofen (10-100 microM) produced a time-dependent shortening of spontaneous action potentials of the guinea-pig renal pelvis and reduced the amplitude and duration of the accompanying phasic contractions. Indomethacin (10 microM) produced comparable effects on the same parameters and significantly reduced the maximal amplitude of depolarization of the pacemaker potential. In the presence of 100 microM (S)-ketoprofen, 100 microM indomethacin promptly suppressed the residual pacemaker potential and contraction.7. Neither (S)-ketoprofen nor indomethacin (10 microM each for 60 min) affected the parameters of action potential and contraction of the guinea-pig ureter evoked by EFS. Both drugs produced a sustained membrane depolarization.8. The present findings demonstrate that stereoselective COX inhibition affects pacemaker potentials and contractility (electromechanical coupling) in the guinea-pig renal pelvis. The modulatory role of endogenous prostanoids involves an amplification of electromechanical coupling in the renal pelvis while excitability, contractility or propagation of impulses along the ureter appear almost independent of prostanoid generation. Previous reports of a total suppression of pyeloureteral motility by indomethacin may reflect a combination of COX inhibition and nonspecific effect on electromechanical coupling.
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PMID:Modulation by stereoselective inhibition of cyclo-oxygenase of electromechanical coupling in the guinea-pig isolated renal pelvis. 762 Jul 4

The role of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) in the upper urinary tract of the guinea-pig and rat was examined using simultaneous tension recordings of the proximal and distal regions of the renal pelvis and the ureter. The guinea-pig upper urinary tract contracted at a frequency (7.52+/-0.3 min(-1) at 35 degrees C) significantly lower than the frequency in the proximal renal pelvis (21.6+/-1.3 min(-1)) and in the distal renal pelvis and ureter (20.2+/-1.4 min(-1)) of the rat (at 30 degrees C). Indomethacin (>/=1 microM for 60 min), decreased the motility index (amplitudexfrequency) (MI) in all three regions of the guinea-pig upper urinary tract, an effect which mainly arose from a decrease in the frequency of contractions. In the rat, indomethacin (1 - 30 microM for 60 min) significantly decreased the MI calculated in the proximal renal pelvis (>/=30 microM indomethacin), and in the distal renal pelvis (>/=10 microM indomethacin), arising from a significant decrease in the amplitude of contractions. The COX-1 inhibitor, valeryl salicylate (VSA) (5 - 100 microM for 60 min), had no effect on either the amplitude or frequency of contractions in the guinea-pig upper urinary tract. In contrast, VSA increased the force of contractions in the proximal and distal renal pelvis of the rat, whilst having little effect on the frequency of contractions. The COX-2 inhibitor, NS-398 (10 - 100 nM for 60 min) reduced the MI in the guinea-pig upper urinary tract in a concentration-dependent manner. The MIs calculated for the proximal renal pelvis, distal renal pelvis and ureter, were decreased by 72, 64 and 72% respectively, in 100 nM NS-398. NS-398 (10 - 100 nM) had no effect on any of the three parameters measured in either the proximal or distal renal pelvis of the rat. These data suggest that endogenously-released prostaglandins (PGs) maintain the myogenic contractility of the upper urinary tract in both the guinea-pig and rat. Moreover COX-2 is the primary enzyme involved in synthesizing PGs in the guinea-pig upper urinary tract, while COX-1 appears to be the predominantly active enzyme in the rat.
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PMID:Effects of selective inhibitors of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) on the spontaneous myogenic contractions in the upper urinary tract of the guinea-pig and rat. 1068 90