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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylate cyclase and phosphodiesterase enzyme activities were demonstrated in rabbit ureter. NaF, 10 mM, caused a 60.9 per cent increase in adenylate cyclase activity. Isoproterenol, 5 X 10-7 to 10-5 M induced a statistically significant dose-dependent increase in adenylate cyclase activity which was suppressed by propranolol, 10-7 M. Theophylline, 5 X 10-5 to 10-2 M, significantly inhibited phosphodiesterase activity. Thus, isoproterenol and theophylline, two agents that can relax ureteral segments previously contracted by a depolarizing concentration of potassium, could presumably increase cyclic AMP levels, isoproterenol by increasing synthesis and theophylline by decreasing degradation.
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PMID:Adenylate cyclase and phosphodiesterase activity in rabbit ureter. 19 62

The effects of specific agonists and antagonists of adrenoceptors and inhibitors of cAMP phosphodiesterase on electrostimulated phasic contractions in the ureter of guinea pig were studied. It has been shown that there mainly excitatory alpha 1-adrenoceptors in this object, the density of beta-adrenoceptors is slight and functional alpha 2-adrenoceptors are probably absent. Some aspects of adrenergic regulation of the contractile function of guinea pig ureter are discussed.
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PMID:[The adrenoreceptor regulation of ureteral contractile function in the guinea pig]. 133 20

Cyclic AMP and cyclic GMP phosphodiesterase (PDE) activities and calmodulin levels were determined in ureters from guinea pigs of the following ages: 50 and 56 days fetuses, three, 10, 21, 50, and 90 days, and three years old. While there is little change in ureteral cyclic AMP-PDE with age, cyclic GMP-PDE increases with age. Activity of cyclic GMP-PDE in supernatants prepared from three-year-old guinea pig ureter homogenates is 462% and 216% higher than that from 50-day fetus and three-day animals, respectively. Calmodulin levels have a bimodal distribution with age; values are highest in supernatants from 10 and 21 day ureters, but also increase in the three-year ureters when compared to 50 and 90-day values.
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PMID:Ontogeny of cyclic AMP and cyclic GMP phosphodiesterase activities and of calmodulin levels in guinea pig ureter. 283 69

Previous studies on the mode of action of flavoxate have shown that the drug exerts a selective and direct muscle relaxant activity. In order to study the mode of action of flavoxate, the following activities were investigated: calcium blocking, inhibition of cyclic AMP phosphodiesterase (PDE), local anaesthetic activity, the effects on the synthesis and release of prostaglandins. In the K+-depolarized guinea-pig taenia coli, contracted by CaCl2, flavoxate and papaverine showed a moderate calcium antagonistic activity. Anticholinergic drugs, such as atropine and emepronium, did not exert a similar action. The antispasmodic activity of a drug can be correlated with inhibition of cyclic AMP phosphodiesterase, and since papaverine is a potent PDE inhibitor, we tested flavoxate for this activity. Flavoxate exerted a PDE inhibitory activity about three and five times greater than that of aminophylline in tissues homogenates of guinea-pig ureter and urinary bladder, respectively. It also showed the same local anaesthetic activity of lidocaine. Finally, the synthesis and release of prostaglandins by urinary bladder muscle in vitro have been investigated before and after treatment with flavoxate. Myolytic activity of papaverine and flavoxate do not involve inhibition of prostaglandins synthesis in rat urinary bladder in vitro. Therefore, the mode of action of flavoxate can be related to a superimposition of myotropic, calcium antagonistic and local anaesthetic activity.
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PMID:Pharmacological studies on the mode of action of flavoxate. 632 16

Phenthiazamine was developed by Sekizawa et al. as a centrally acting anesthetic for fish. Frog sympathetic ganglion was used as a model to elucidate the mechanism of its anesthetic action. The positive ganglionic potential was enhanced immediately after application; then, the potential and the late negative ganglionic potential were markedly reduced by an anesthetic concentration of this compound. The hyperpolarization caused by 1 mM dopamine was enhanced by phenthiazamine. This enhancement of dopamine hyperpolarization and of the positive ganglionic potential may coincide with the fact that cyclic adenosine monophosphoric acid (cAMP) phosphodiesterase was inhibited by the compound as shown in our previous paper. Guinea-pig ileum contraction elicited by electrical field stimulation and by dimethyl-phenyl-piperadinium (DMPP) was reduced by a similar concentration of this compound, while the contraction elicited by acetylcholine and methacholine was not inhibited. The inhibition of contraction elicited by electrical field stimulation and DMPP may thus due to inhibition of acetylcholine release by this compound. The inhibition of ileum contraction by this compound was reversed by higher doses of Ca2+ (5.5 mM). The time required to reduce the positive ganglionic potential in the sympathetic ganglion by phenthiazamine was prolonged in the presence of higher concentrations of Ca2+. The Ca2+-dependent action potential of guinea-pig ureter was reduced by this compound, whereas it did not affect the Na+-dependent action potential.
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PMID:Pharmacological analysis of the mechanism of action of phenthiazamine, a piscine anesthetic. 697 Aug 7

An increase in cyclic nucleotide monophosphate levels is suggested to play a prominent role in mediating smooth-muscle relaxation. Cyclic nucleotide phosphodiesterase (PDE) influences smooth-muscle tone by decreasing the level of cyclic nucleotides. At present, five different families of isoenzymes of PDE exist that show a distinct species- and organ-specific distribution. Our study was done to evaluate the existence of specific PDE isoenzymes and its functional role in human ureteral tissue. Normal ureteral tissue was homogenized and centrifuged and the supernatant fraction was separated using anioin-exchange diethylaminoethyl (DEAE)-Sephacel chromatography. A PDE assay was then performed and the peak fractions were added to different specific PDE activators and inhibitors. In vitro, longitudinal ureteral strips were precontracted and different selective and non-selective PDE inhibitors were added incremently. Three different PDE isoenzymes were characterized: PDE I (calmodulin-sensitive), PDE II (cGMP-stimulated), and PDE IV (cAMP-specific). All PDE inhibitors relaxed the strips dose-dependently, with the 50% effective concentrations (EC50) being 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low-level effect on the systemic circulatory parameters, may open the possibility of using selective PDE IV-inhibitors in the treatment of ureteral colics or for ureteral stone passage.
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PMID:Characterization of cyclic nucleotide phosphodiesterase isoenzymes in the human ureter and their functional role in vitro. 786 26

1. The aim of this study was to assess whether agents that interfere with the intracellular actions of cAMP and activation of protein kinase A (PKA) prevent the inhibitory action of human alpha-calcitonin gene-related peptide (CGRP) in the guinea-pig ureter smooth muscle. The action of CGRP was compared to that of the K+ channel opener, cromakalim, and the adenylyl cyclase activator, forskolin, toward electrical field stimulation- (EFS) induced myogenic twitch contractions of the ureter. To further verify the role of cAMP in the action of CGRP, we also studied the effect of stable cAMP analogues and of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). 2. Maximally effective concentrations of CGRP (0.1 microM) or forskolin (10 microM) produced a transient suppression of twitches. Cromakalim (3 microM) likewise produced a prompt suppression of twitches that in most cases exceeded 15 min. The early suppressant effect of CGRP or forskolin was inhibited by 1 or 10 microM glibenclamide; about 30% of the effect of CGRP was glibenclamide-resistant. The effect of cromakalim was totally suppressed by glibenclamide. 3. The inhibitory effect of CGRP was concentration-dependently reduced by low concentrations of barium chloride (IC50 63 microM), which blocked with similar potency the inhibitory action of cromakalim (IC50 60 microM). Glibenclamide (10 nM-10 microM) concentration-dependently inhibited the effect of CGRP and cromakalim with IC50S of 0.13 and 0.72 microM, respectively. 4. The cAMP analogues dibutyrye-cAMP (1-3 mM), 8-(4-chlorophenylthio)cAMP (0.3-1 mM) and Sp-cAMP monophosphothioate (0.1-0.3 mM) were either ineffective or poorly effective in inhibiting twitches. The cGMP analog, 8Br-cGMP (100-300 microM) produced a slowly developing, glibenclamide (1 microM)-resistant partial inhibition (25-30%) of twitches. 5. IBMX (1-300 microM) produced a concentration-dependent inhibition of twitches (EC50 16 microM). IBMX (100 microM) produced a large (peak 91%) and transient inhibition: glibenclamide (1 microM) blocked the early peak of the inhibitory action of IBMX, similar to the effect observed toward CGRP and forskolin.
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PMID:Role of cyclic AMP and protein kinase A in K+ channel activation by calcitonin gene-related peptide (CGRP) in the guinea-pig ureter. 874 80

Literature search and in vitro studies on ureteral function in humans and rabbits have proven that the rabbit is a suitable animal model for the investigation of the effect of smooth muscle relaxing substances on the ureter. One of the main problems encountered was to find an appropriate anesthetic protocol for this animal model. Application of barbiturates as a monotherapy proved to be unsuitable to allow painfree preparation of the abdomen. Intravenous (iv) anesthesia consisting of ketamine-HCl/xylazine-HCl could not be considered due to interference with ureteral smooth muscle tone. Intravenous administration of ketamine-HCl induced immediate ureteral contractions with increased frequency of ureteral activity. Xylazine-hydrochloride, a mixed alpha 2-, alpha 1-adrenoceptor agonist inhibits the increase in synthesis of 3'5'-cAMP. Since the test substances used are phosphodiesterase-IV-inhibitors (rolipram and its two enantiomers), which increase 3'5'-cAMP, this type of anesthesia would interfere with the pharmacological effect to be investigated. General anesthesia using a combination of nitrous oxide (2 l/min) and oxygen (1 l/min) and a very small amount (2 mg/kg b.w.) of pentobarbital i.v. every 30 minutes, was found to be the most suitable form of anesthesia. It resulted in much more stable circulatory conditions, sufficient depth of anesthesia and the possibility to test muscle relaxing substances (PDE-IV-inhibitor) without any influence from anesthesia on their efficacy.
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PMID:General anesthesia for ureteral measurements in the rabbit. 922 67

1. The mechanisms and receptors involved in the vasoactive intestinal peptide (VIP)- and pituitary adenylate cyclase-activating polypeptide (PACAP)-induced relaxations of the pig intravesical ureter were investigated. 2. VIP, PACAP 38 and PACAP 27 concentration-dependently relaxed U46619-contracted ureteral strips with a similar potency. [Ala(11,22,28)]-VIP, a VPAC(1) agonist, showed inconsistent relaxations. 3. The neuronal voltage-gated Ca(2+) channel inhibitor, omega-conotoxin GVIA (omega-CgTX, 1 microm), reduced the VIP relaxations. Urothelium removal or blockade of capsaicin-sensitive primary afferents, nitric oxide (NO) synthase and guanylate cyclase with capsaicin (10 microm), N(G)-nitro-l-arginine (l-NOARG, 100 microm) and 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 microm), respectively, did not change the VIP relaxations. However, the PACAP 38 relaxations were reduced by omega-CgTX, capsaicin, l-NOARG and ODQ. 4. The VIP and VIP/PACAP receptor antagonists, [Lys(1), Pro(2,5), Arg(3,4), Tyr(6)]-VIP (1 microm) and PACAP (6-38) (0.4 microm), inhibited VIP and VIP and PACAP 38, respectively, relaxations. 5. The nonselective and large-conductance Ca(2)-activated K(+) channel blockers, tetraethylammonium (3 mm) and charybdotoxin (0.1 microm), respectively, and neuropeptide Y (0.1 microm) did not modify the VIP relaxations. The small-conductance Ca(2)-activated K(+) channel blocker apamin (1 microm) did not change the PACAP 27 relaxations. 6. The cAMP-dependent protein kinase A (PKA) blocker, 8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate (Rp-8-CPT-cAMPS, 100 microm), reduced VIP relaxations. The phosphodiesterase 4 inhibitor rolipram and the adenylate cyclase activator forskolin relaxed ureteral preparations. The rolipram relaxations were reduced by Rp-8-CPT-cAMPS. Forskolin (30 nm) evoked a potentiation of VIP relaxations. 7. These results suggest that VIP and PACAP relax the pig ureter through smooth muscle receptors, probably of the VPAC(2) subtype, linked to a cAMP-PKA pathway. Neuronal VPAC receptors localized at motor nerves and PAC(1) receptors placed at sensory nerves and coupled to NO release, seem also to be involved in the VIP and PACAP 38 relaxations.
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PMID:Heterogeneity of neuronal and smooth muscle receptors involved in the VIP- and PACAP-induced relaxations of the pig intravesical ureter. 1466 37

Cyclic nucleotide levels are controlled through their synthesis from nucleotide triphosphates by cyclases and their degradation to 5'-monophosphates by phosphodiesterases (PDEs). Components controlling cyclic AMP-induced relaxation in the urinary tract include receptors, inhibitory and stimulatory G-proteins, isoforms of adenylyl cyclase and PDEs. The responsiveness of PDEs to a variety of physiological challenges is related to the presence of multiple families of isoenzymes with specific localization within tissues and within cells. At least 11 families of PDEs encode more than 50 PDE proteins produced in mammalian cells. In the urinary tract, characterization of PDE isoforms has lagged behind other systems and much of the literature was published prior to identification of PDE7, 8, 9, 10, 11. Specific PDE inhibitors regulate smooth muscle function in the bladder, urethra, prostate and ureter. The pharmacological potential of these inhibitors may include treatment of urge incontinence and the low compliance bladder, and treatment of prostate cancer. G-proteins also regulate cyclic AMP production. Changes in specific G- protein isoforms with aging, most prominently Gialpha2, cause decreased relaxation response in the aging bladder. As we have seen here with aging and certainly in other disease processes, levels of the components of adenylyl cyclase/phosphodiesterase/protein kinase can change and thus affect the relaxation response. By exploitation of differences in PDE expression in disease, such as the overexpression of PDEs in cancer, treatment options may present themselves.
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PMID:Regulation of cyclic nucleotides in the urinary tract. 1585 36


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