The mode of action of prostaglandin E2, F2 alpha and prostacyclin on vesicourethral smooth muscle

Interactions of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha) and prostacyclin (PGI2) with Ca2+ on the isometric contraction of rabbit detrusor muscle strips were studied using two types of Ca2+ antagonists of different mechanisms of action: verapamil and sodium nitroprusside (NP). The effects of PGI2 on vesicourethral smooth muscle and their relationship with cholinergic, adrenergic receptors and nervous activity were also investigated. PGE2 and F2 alpha (3 X 10(-8) to 3 X 10(-5) M) caused dose-dependent contraction of the strips. Pretreatment of the strips with verapamil (10(-7) to 10(-5)M) significantly inhibited PGs-induced contraction in a dose-dependent manner, whereas NP(10(-7) to 10(-5)M) failed to suppress the contraction. Relaxation of the preparations once contracted by PGE2 and F2 alpha (3 X 10(-6)M) was induced completely by addition of verapamil (10(-5)M), and incompletely by NP(10(-5) to 10(-3)M). Washing of the strips with Ca2+-free solution containing 0.01 mM EGTA completely eliminated spontaneous activity and diminished basal tension, but replenishment of Ca2+ (0.5 to 10 mM) to the medium caused dose-related contraction and spontaneous activity of the strips. Addition of PGE2 and F2 alpha to the Ca2+-free medium enhanced Ca2+-induced contraction and spontaneous activity during Ca2+ replenishment, which were significantly inhibited by pretreatment with verapamil (10(-7) to 10(-5)M) in a dose-dependent manner, but not affected by NP (10(-7) to 10(-5)M). In Ca2+-free medium containing 0.1 mM EGTA, PGE2 and F2 alpha caused a slight degree of tension increase of the strips dose-dependently at the higher concentration exceeding 3 X 10(-6)M. PGI2 (10(-9) to 3 X 10(-4)M) caused dose-dependent contraction of the strips from the bladder body, base and the urethra. The contractile action of PGI2 was greatest on the bladder body, less on the base and minimal on the urethra. The effect of PGI2 was less potent than those of PGE2 and F2 alpha. The PGI2-induced contraction was slow in onset, short lasting, and not affected by pretreatment with phentolamine, propranolol, atropine, hexamethonium, hemicholinium-3 and tetrodotoxin. The interactions of PGI2 with Ca2+ were similar to those of PGE2 and F2 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)     

Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery

Contractant and relaxant effects of prostaglandins (PG) F2 alpha, E1 and E2, prostacyclin (PGI2), the thromboxane A2 agonist U46619 and the prostaglandin endoperoxide analogue U44069 were investigated in isolated preparations of the human corpus cavernosum, corpus spongiosum and cavernous artery. In corpus cavernosum and corpus spongiosum preparations, PGF2 alpha produced concentration-dependent contractions showing rhythmic variations in tension. The contractions were effectively relaxed by carbachol and vasoactive intestinal polypeptide. U46619, U44069 and PGI2 also contracted corpus cavernosum and corpus spongiosum strips at resting tension, U46619 being the most potent drug. PGE1 and PGE2, but not PGI2 relaxed corpus cavernosum and corpus spongiosum preparations contracted by noradrenaline (NA) and PGF2 alpha. PGE1 was the more effective agent; high concentrations of PGE2 produced contraction. In cavernous artery segments, PGF2 alpha produced concentration-dependent contractions. No oscillations in tension were observed; carbachol had no relaxant action, but VIP effectively relaxed the vessels. U46619 and U44069, but not PGI2 had contractant effects on cavernous artery segments at resting tension. PGE1 and PGI2, but not PGE2 relaxed NA contracted vessel preparations; all agents (PGE2 less effectively) relaxed PGF2 alpha contracted vessel segments. It is concluded that cavernous artery and erectile tissue proper (corpus cavernosum and corpus spongiosum) differ importantly in their reaction to various prostanoids. It cannot be excluded that products of the arachidonate cascade can be involved in the control of penile tumescence and erection.     

Prostaglandin type E activity dominates in urinary tract smooth muscle in vitro

Changes in isometric tension and spontaneous contractions in human and porcine lower urinary tract smooth muscle strips caused by PGE2, PGF2a and the prostaglandin biosynthesis inhibitor ketoprofen were investigated in vitro. Ketoprofen reduced the prostaglandin biosynthesis significantly and caused reversible and dose dependent decreases of tension and spontaneous contractions in detrusor strips, while tension increase was induced in strips from the urethra, bladder neck and trigone. PGE2 reestablished the tension and the spontaneous activity in the detrusor strips and counteracted the tension increase in strips from the urethra, bladder neck and trigone. PGF2a increased the tension in all strips. The threshold concentration for prostaglandin effect in strips pretreated with ketoprofen was 10(-10) - 10(-9) mol./l., a concentration which might be considered physiologically relevant. Prostaglandin synthesis inhibition thus caused responses opposite to those of PGE2 in every single strip. These results strongly suggest the PGE-type of activity to be more important than the PGF-type of activity in lower urinary tract smooth muscle in vitro.     

The actions of prostaglandins on the smooth muscle of the human urinary tract in vitro.

14 experiments, 10 on bladder muscle strips and 4 on samples of ureteric muscle, were performed to examine the actions of 4 prostaglandins (PGE, PGE2, PGF1alpha and PGF2alpha) on these tissues. Each of the prostaglandins caused bladder muscle to contract and prostaglandin F2alpha was the most potent in this respect. The F series prostaglandins also caused increased ureteric muscle contraction whilst those of the E series inhibited contractions. It is unlikely that contraction is produced by the direct action of prostaglandins on urinary smooth muscle. The suggestion is made that prostaglandins may have a function in the maintenance of vesical tone.     

Comparison of the effects of primary prostaglandins on isolated human urinary bladder

The effects of primary prostaglandins (PGs) on the dome and trigone of the human urinary bladder were investigated in vitro. In the dome preparations, PGE1 (10(-9) to 10(-6) gm./ml.) showed a weak contractile effect, while PGE2 (10(-9) to 10(-6) gm./ml.) produced dose-dependent contractions. PGF2 alpha (10(-9) to 10(-6) gm./ml.) induced contractions greater than those induced by PGE1 and PGE2. In the trigone preparations, PGE1 (10(-9) to 10(-6) gm./ml.) had no effect, and PGE2 (10(-9) to 10(-6) gm./ml.) produced only a weak contractile response. PGF2 alpha (10(-9) to 10(-6) gm./ml.) showed a greater contractile potency than PGE2. Contractile responses of both preparations to PGE1, PGE2 and PGF2 alpha were not affected by pretreatments of atropine, hexamethonium and phentolamine. These results suggest that the order of potency of primary PGs to induce contractile responses is PGF2 alpha greater than PGE2 greater than PGE1 in both the dome and the trigone preparations, and that the contractile effects of PGE1, PGE2 and PGF2 alpha may not be mediated by activation of muscarinic, nicotinic or adrenergic alpha-receptors.     

Age-related changes in contractile force of rabbit detrusor muscle to prostaglandin E1, E2 and F2 alpha

Contractile responses of urinary bladder muscle strips to prostaglandin (PG) E1, E2 and F2 alpha were compared in young and old rabbits. All PGs tested caused an increase in contractile force of urinary bladder muscle strips from young (3 weeks) and old (greater than 2 years) rabbits. The contractile response was most marked with PGE2 at concentrations of 10(-10)-10(-7) M in muscle strips from both young and old rabbits. At a high concentration (10(-5) M), the contractile response was most marked with PGF2 alpha in young rabbit bladder muscle strips, whereas in old rabbit bladder muscle strips the magnitude of the responses to PGE2 and PGF2 alpha were equal at 10(-6) M and both were greater than the response to PGE1. The contractile response to PGE1 was greater in old detrusor than in young detrusor at concentrations greater than or equal to 10(-6) M, whereas the contractile response to PGE2 (10(-7)-10(-5) M) and PGF2 alpha (10(-6)-10(-5) M) were greater in young detrusor than in old detrusor. These data show that rabbit detrusor muscle shows a contractile response to PGE1, E2 and F2 alpha and that the magnitude of these responses vary with age.     

Nociceptin/orphanin FQ alters prostaglandin cerebrovascular action following brain injury

Previous studies have observed that fluid percussion brain injury (FPI) elevated the CSF concentration of the opioid nociceptin/orphanin FQ (NOC/oFQ). In separate studies, FPI impaired pial artery dilation to the prostaglandins PGI2 and PGE2. This study was designed to investigate the following: (1) role of NOC/oFQ in impaired dilation to PGI2 and PGE2, (2) the effects of FPI on vasoconstriction to the TXA2 mimic U46619 and PGF2alpha, and (3) the role of NOC/oFQ in such FPI induced effects on U46619 and PGF(2alpha). Lateral FPI was induced in newborn pigs equipped with a closed cranial window. PGI2 (1, 10, 100 ng/ml) vasodilation was blunted by FPI and fully restored by the NOC/oFQ antagonist, [F/G] NOC/oFQ (1-13) NH2 (10(-6)M) (9 +/- 1, 13 +/- 1, and 19 +/- 1 vs. 2 +/- 1, 4 +/- 1, and 5 + 1 vs 7 +/- 1, 12 +/- 2, and 17 +/- 3% for control, FPI, and FPI + [F/G] NOC/oFQ (1-13) NH2, respectively). Similar effects were observed for PGE2. In contrast, U46619 (1, 10 ng/ml) induced vasoconstriction was potentiated by FPI but returned to the response observed prior to FPI by [F/G] NOC/oFQ (1-13) NH2 ( -8 +/- 1 and -14 +/- 1 vs. -15 +/- 1 and -25 +/- 1 vs. -7 +/- 1 and -12 +/- 2% for control, FPI, and FPI + [F/G] NOC/oFQ (1-13) NH2, respectively). Similar effects were observed for PGF(2alpha). Coadministration of NOC/oFQ (10(-10)M), the CSF concentration observed after FPI, with agonists under nonbrain injury conditions blunted PGI2 and PGE2 vasodilation, but potentiated U46619 and PGF2alpha vasoconstriction similarly to that observed after FPI. These data show that FPI blunted PGI2 and PGE2 vasodilation but potentiated U46619 and PGF2alpha vasoconstriction. Additionally, these data show that administration of a NOC/oFQ receptor antagonist prevented such FPI associated events. NOC/oFQ administrated in a concentration observed after FPI produced blunted dilator prostaglandin and potentiated vasoconstriction prostaglandin vascular responses under nonbrain injury conditions. Finally, these data suggest that NOC/oFQ alters prostaglandin cerebrovascular action following brain injury.     

Effects of highly concentrated estrogen and progesterone on the contractile mechanism of the uterine smooth muscles

The effects of a high concentrated estrogen and progesterone were studied on the contractile activities in isolated myometrial strips from humans and rats by recording isometric tension development. The contractions were reduced by 10(-5)-3 X 10(-5) M estrone (E1), estradiol (E2), estriol (E3), and progesterone (P) in non pregnant human uterus. The contractions were reduced by 10(-6)-10(-4) M E1, E2, E3 and P in non pregnant rat uterus. The contractions induced by 10(-8)-10(-5) M PGE2 and PGF2 alpha were reduced by 10(-5) M E2 and P in non pregnant rat uterus. The contractions induced by 10(-10)-3 X 10(-8) M oxytocin were reduced by 10(-5) M E2 and P in non pregnant rat uterus. The contractures induced by 10(-4)-10(-2) M Ca2+ were reduced by 10(-5) M E2 and P in non pregnant rat uterus. The effects of a high concentrated estrogen and progesterone were studied on Ca2+ influx and Ca2+ release from intracellular Ca store in the depolarized uterine smooth muscle cells from non pregnant rats. The inhibitory effects on the contractility by 3 X 10(-6)-3 X 10(-5) M E2, E3 and P supported the suggestion that estrogen and progesterone have an inhibitory action on Ca2+ influx and Ca2+ release from intracellular Ca store.     

Roles of prostaglandin on rabbit vesicourethral smooth muscle contraction]

The effects of prostaglandin (PG) E1, E2 and F2 alpha on isolated smooth muscles of rabbit bladder and urethra were studied by in vitro techniques for recording contractile activities. To examine the mechanism of PGs' effect, intracellular cyclic AMP content was also measured by radioimmunoassay. Spontaneous contractile force of muscle strips isolated from rabbit urinary bladder dome and base was increased dose-dependently by administration of PGE1, E2 or F2 alpha. Isolated muscle strips from bladder dome responded to PG more markedly than those from bladder base. The rank order of potency to induce contractile responses was PGF2 alpha greater than PGE2 greater than PGE1 in both dome and base muscles. Spontaneous contractile force of muscle strips isolated from rabbit urethra was increased dose-dependently by administration of PGF2 alpha, and, in contrast, was decreased dose-dependently by PGE1 or E2. These effects were not affected by pretreatment with atropine, phentolamine, propranolol and tetrodotoxin, but were significantly inhibited by pretreatment with verapamil, a Ca-antagonist. Cyclic AMP accumulation in urethral muscle strips significantly increased after administration of PGE1. These results demonstrated that contractile response of rabbit bladder smooth muscle to PG was mainly induced by Ca2+ influx and that cyclic AMP was related to the relaxation of rabbit urethral smooth muscle by PGE1.     

Effects of prostaglandins on the contractile mechanism, especially on an intracellular Ca store in uterine smooth muscle cells

The effects of prostaglandins were studied on the contractile activities in isolated myometrial or vaginal strips from humans and rats by recording isometric tension development. PGE2 decreased the contractility in corpus and cervix from non pregnant human uterus, but increased the contractility in corpus and decreased the contractility in cervix from term human uterus. PGF2 alpha increased the contractility in corpus and cervix from non pregnant and term human uterus. PGE2 increased the contractility in corpus, but decreased the contractility in cervix and vagina from non pregnant and term rats. PGF2 alpha increased the contractilities in corpus, cervix and vagina from non pregnant and term rats. The effects of prostaglandins were studied on an intracellular Ca store in the depolarized uterine smooth muscle cells from non pregnant rats. The activative effects on the contractile mechanism by prostaglandins supported the suggestion that prostaglandins have an activative action on Ca2+ influx and Ca2+ release from intracellular Ca store. The inhibitory effects on the contractile mechanism by PGE2 supported the suggestion that PGE2 have an inhibitory action on Ca2+ influx and Ca2+ release from intracellular Ca store.     

Effects of calcium and verapamil on vesicourethral smooth muscle of rabbits

Isolated smooth muscle strips from the rabbit bladder body, bladder base, and proximal urethra were contracted with ionic calcium (Ca2+) alone and with the calcium-selective ionophore A23187, acetylcholine, norepinephrine, adenosine triphosphate (ATP), and direct electrical stimulation. The effects of Ca2+ and the calcium entry blocker verapamil on spontaneous muscle activity and on contractions induced by these agonists were examined. Ca2+ -free Tyrode's solution and verapamil, 1 x 10(-7)M and above, relaxed all of the vesicourethral smooth muscle strips. In addition verapamil, 1 x 10(-8) to 1 x 10(-6) M depending on the particular stimulant employed, noncompetitively inhibited smooth muscle contractions elicited by Ca2+, acetylcholine, norepinephrine, ATP, and direct electrical stimulation. It was concluded that transmembrane Ca2+ influx was important not only in the maintenance of tone and spontaneous phasic muscle activity, but also for the activation of contractions induced by all of the stimulants tested. The data also suggest that intracellular Ca2+ fraction(s) participate in the contractile responses to acetylcholine and norepinephrine challenge, but not to contractions evoked by ATP or electricity.     

Regulation of prostaglandin synthesis by reduced glutathione in urinary bladder epithelium

A possible mechanism is presented by which reduced glutathione (GSH) regulates prostaglandin (PG) synthesis in microsomes of the porcine bladder epithelium. At a concentration of GSH less than 10(-5) M, microsomes produced more PGI2 and PGF2 alpha than PGE2. At a greater GSH concentration, PGE2 synthesis was remarkably enhanced. On the other hand, PGI2 and PGF2 alpha synthesis was inhibited. In the presence of 10(-3) M GSH, ten times more PGE2 was produced than the other PGs. The concentration of GSH in porcine bladder epithelium was about 0.6 mM. This reciprocal effect of GSH was also observed in rabbit and bovine bladder epithelium. These findings suggest that GSH is involved in the regulation of PG synthesis in urinary bladder epithelium. GSH may influence the physiological and pathophysiological changes elicited by PGs in the lower urinary tract.     

Regulation of rat caput epididymidis contractility by prostaglandins

Mechanical activity of the rat caput epididymidis in vitro was recorded using a videomicrography system. The effects of prostaglandin (PG)F2 alpha, PGE2, and aspirin on caput epididymidis contractility were determined by measuring the frequency of contraction, luminal diameter, and amplitude of contraction at various concentrations of each test compound in vitro. PGF2 alpha stimulated contractility of the tubules at physiological concentrations, while PGE2 reduced contractility. Aspirin strongly inhibited contractility at concentrations of 10(-3) and 10(-2)M. Endogenous levels of PGF2 alpha and PGE were determined for rat testes, caput, corpus, and cauda epididymidis and vas deferens. While the concentrations of PGE were consistently higher than those of PGF2 alpha, both compounds were relatively low in the testes, high in the vas deferens, and intermediate throughout the epididymis. Results from these experiments strongly suggest that PGs are important regulators of proximal epididymidis contractions and thus may regulate sperm transport through that organ.     

Eicosanoid synthesis by human urinary bladder mucosa: pathological implications

Biopsies of human urinary bladder mucosa obtained during cystoscopy were shown to release eicosanoids in the following order: prostacyclin (PGI2), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TXA2). The total and the relative amounts of eicosanoids released were similar to those reported for the rat urinary bladder. These eicosanoids may play a role in modulating the tone and contractility of the bladder as well as affecting cytoprotection of the mucosa. In view of the abundant release of eicosanoids by the bladder, caution must be exercised when considering urinary eicosanoid excretion as reflecting production by the systemic vasculature and/or the kidneys.     

Effects of disopyramide on detrusor muscle contraction: in vitro experiment and report of 3 cases with disopyramide-induced urinary retention

Three cases of disopyramide-induced urinary retention were reported and effects of disopyramide on agonist-induced contraction of detrusor muscle were studied in vitro. Muscle strips were obtained from rabbit bladder body and changes in isometric contraction of the strips were monitored. Acetylcholine, prostaglandin F2-alpha, potassium chloride, barium chloride, adenosine triphosphate and Ca2+ were used as agonists for detrusor muscle contraction. Disopyramide relaxed the contraction elicited by acetylcholine in normal Krebs solution, but exhibited no relaxing effect on contractions induced by prostaglandin F2-alpha, potassium chloride, barium chloride and adenosine triphosphate. In Ca2+-free Krebs solution, basal tension of the strips declined and spontaneous contractile activity was eliminated. Replenishment of 3 mM Ca2+ induced a slow contraction and redevelopment of spontaneous contraction of the strips. Pretreatment of the strips with disopyramide had no inhibitory effect on the Ca2+-induced contraction or on the spontaneous contractile activity in Ca2+-free solution. In normal Krebs solution, acetylcholine (10(-9)-10(-2)M) caused dose-dependent contractions of the detrusor muscle strips. Pretreatment of the strips with disopyramide (10(-5)-10(-3)M) dose-dependently inhibited the acetylcholine-induced contraction in a competitive way. The inhibitory effect of disopyramide on acetylcholine-induced contraction was less potent than that of atropine. We conclude that disopyramide may inhibit detrusor contractile activity mostly by its anticholinergic effect, resulting clinically in micturition disturbance.     

The regulation and role of prostaglandin biosynthesis in cultured bovine glomerular endothelial cells

The experiments described in this article were designed to investigate the regulation of, and functional response to, prostaglandin (PG) synthesis in cultured bovine glomerular endothelial cells. Glomerular endothelial cells in culture synthesized PGE2 much greater than PGF2 alpha greater than thromboxane A2 greater than PGI2 in the presence of 30 microM arachidonate. Basal levels of PGE2 synthesis in these cells were one sixth less than that of bovine mesangial cells. PGE2 synthesis was time dependent and required the continuous presence of serum. Moreover, PGE2 synthesis was regulated by phospholipase A2 as shown by ionomycin-stimulated PGE2 accumulation as well as by bradykinin- and thrombin-stimulated PGE2 accumulation. Even though acidic fibroblast growth factor and heparin were required to support glomerular endothelial cell growth in culture, these agents downregulated PGE2 synthesis. PG endoperoxide synthase activity, as shown by arachidonate-stimulated PGE2 accumulation, also regulated PGE2 synthesis. PGE2 and PGF2 alpha, as well as thromboxane A2 and PGI2 mimetics (1 microM) evoked mitogenesis in quiescent glomerular endothelial cells. PGE2 and PGF2 alpha were most potent, and threshold doses of these PG were 10 nM. These data suggest that glomerular endothelial cells are similar to other microvascular endothelial cells in their regulation of PG synthesis and that, under physiological conditions, the proliferation of glomerular endothelial cells might be regulated by PG in an autocrine or paracrine fashion.     

Comparison of prostanoid synthesis in cultured human vascular endothelial cells derived from omentum and umbilical vein

Endothelial seeding of vascular grafts may reduce thrombogenicity and significantly improve graft patency. For clinical studies endothelial cells derived from human omentum may be the ideal source of cells as they are obtainable in large numbers. This study was designed to assess their ability to produce the antithrombogenic substance prostacyclin (PGI2). Human omental microvascular endothelial cells (HOTMECs) were grown and their ability to produce prostacyclin (PGI2), PGE2, PGF2 alpha and thromboxane A2 (TXA2) in response to a range of agonists was measured by radioimmunoassay. Control experiments were performed using human umbilical vein endothelial cells (HUVECs). Both HUVECs and HOTMECs synthesised similar quantities of PGI2 basally and both increased production after adding A23187 (calcium ionophore), arachidonic acid, sodium fluoride and phorbol ester. In contrast, both thrombin and histamine were potent stimulators of PGI2 release in HUVECs but were without effect on HOTMECs. In both cell types serotonin, carbachol and noradrenaline were without effect. The pattern of release of PGE2, PGF2 alpha and TXA2 were identical to those of PGI2 in both cell types but the quantities released were lower. These results show that HOTMECs can produce the antithrombogenic agent PGI2 in significant quantities and that they do so by mechanisms similar to those of large vessel endothelium. This supports the proposal that they would be a suitable cell source for vascular graft seeding.     

Response of the rabbit isolated testicular capsule at hypothermic and hyperthermic temperatures to norepinephrine, acetylcholine and prostaglandin F2 alpha

Spontaneous contractions of the adult rabbit isolated testicular capsule were found to be influenced by moderate hyperthermic and hypothermic temperature changes. The decrease in testicular capsular spontaneous contractions resulting from an exposure to 32, 40 and 42 degrees C have been shown to be influenced by the addition of NE, ACh and PGF2 alpha. Of the three neurohumoral agents studied, NE was found to cause the greatest increase and re-initiation of testicular capsular tone during both hypothermia and hyperthermia. These data indicate that endogenous levels of neurohumoral agents may play an important role in the maintenance of testicular capsular tone during exposure to hyperthermic or hypothermic conditions.     

Selective augmenting effect of oxy-Hb on the contractions of cerebral arteries elicited by various vasoactive substances

Serotonin (5-HT), histamine (HA), angiotensin II (ATII), prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TxA2) are known as vasoactive substances, each producing a characteristic contraction of cerebral arteries. These contractions are considered to be mediated by their specific receptors. Recent studies suggest that the activations of these receptors primarily stimulate the phospholipase C and/or phospholipase A2 localized within the same membrane. Stimulation of these enzymes consequently induces production of the second or third messengers such as inositol triphosphate (IP3), diacylglyceride (DAG), arachidonic acid (AA), and ultimately various prostaglandins. The present study is to examine how oxyhemoglobin (Oxy-Hb), another vasoactive substance, can modify these receptor-mediated contractions, and to compare the effects on high K+-, caffeine-and 1-oleoyl-2-acetyl-rac-glycerol (OAG)-induced contractions which are not mediated by the receptors on the cytoplasmic membrane. Helical strips of the bovine middle cerebral arteries (M2) were mainly used in this experiment, and the changes in muscular tensions during isometric contractions were recorded on the polygraph. 5-HT, HA, ATII, PGF2 alpha and cTxA2 (carbocyclic thromboxane A2) were used for each receptor activation. Indomethacin (IDM), a cyclooxygenase inhibitor and 2-nitro-4-carboxyphenyl-n, n-diphenyl-carbamate (NCDC), a phospholipase C inhibitor were used to analyze a possible acting site of Oxy-Hb in modifying these reseptor-mediated enzyme reactions. The results obtained are summarized as follows. (1) All contractions induced by either 5-HT, PGF2 alpha, cTxA2, HA or ATII (concentrations less than 10(-6) M) were markedly augmented as much as 4-8 times the normal, when they were examined in the presence of 10(-5)M Oxy-Hb.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder

PURPOSE: NGF and PGs in the bladder can be affected by pathological changes in the bladder and these changes can be detected in urine. We investigated changes in urinary NGF and PGs in women with OAB. MATERIALS AND METHODS: The study groups included 65 women with OAB and 20 without bladder symptoms who served as controls. Evaluation included patient history, urinalysis, a voiding diary and urodynamic studies. Urine samples were collected. NGF, PGE2, PGF2alpha and PGI2 were measured using enzyme-linked immunosorbent assay and compared between the groups. In addition, correlations between urinary NGF and PG, and urodynamic parameters in patients with OAB were examined. RESULTS: Urinary NGF, PGE2 and PGF2alpha were significantly increased in patients with OAB compared with controls (p <0.05). However, urinary PGI2 was not different between controls and patients with OAB. In patients with OAB urinary PGE2 positively correlated with volume at first desire to void and maximum cystometric capacity (p <0.05). Urinary NGF, PGF2alpha and PGI2 did not correlate with urodynamic parameters in patients with OAB. CONCLUSIONS: NGF and PGs have important roles in the development of OAB symptoms in female patients. Urinary levels of these factors may be used as markers to evaluate OAB symptoms.