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Phasic Contractions (phasic + contraction)
Selected AbstractsExpression of Rho-kinase and its functional role in the contractile activity of the mouse vas deferensBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Kansu Büyükaf The effects of two Rho-kinase inhibitors, Y-27632 and fasudil, were investigated on the contractions produced by electrical field stimulation (EFS, 40 V, 1 mS, 2, 4, 8 and 16 Hz, for 20 s), KCl (30 , 60 mM), phenylephrine (Phe) (10,5 , 10,4M), adenosine-3,, 5,-triphosphate (ATP) (10,4 , 10,3M) and ,,, -methylene ATP (10,5M). EFS produced frequency-dependent reproducible contractile activity, which was almost abolished by guanethidine (10,5M, for 1 h). This contraction consisted of two components (a phasic initial contraction followed by a tonic one), and it was inhibited by Y-27632 and fasudil (both at 10,5M). However, these inhibitors had no effect on resting tension of the tissue. Contractions elicited by KCl (30 , 60 mM) were insensitive to guanethidine (10,5M, for 1 h), but suppressed by Y-27632 (10,5M) and fasudil (10,5M). In addition, the contractions induced by Phe (an ,1 -adrenoceptor agonist) and ATP (a purinergic agent) were inhibited significantly by Y-27632 (10,5M). Phasic contractions evoked by the selective P2X purinoceptor agonist ,,, -methylene ATP were also suppressed by Y-27632 (10,5M). Western blot analysis revealed that the mouse vas deferens expresses Rho-kinase (ROK,, ROCK-2 isoform) protein with a molecular weight of approximately 160 kDa. As a positive control, the presence of this protein was also shown in homogenates of smooth muscle from the rat mesenteric artery. In conclusion, Rho-kinase protein is expressed in the mouse vas deferens, and it mediates neurogenic contractile activity as well as the contractions induced by KCl, Phe, ATP and ,,, -methylene ATP. Owing to the suppressive effects of Rho-kinase inhibitors on the contractile activity of the vas deferens, the possibility that these compounds might impair ejaculation must be taken into account when considering them as potential agents in the treatment of erectile dysfunction. British Journal of Pharmacology (2003) 140, 743,749. doi:10.1038/sj.bjp.0705479 [source] Microinjection of glutamate into dorsal motor nucleus of the vagus excites gallbladder motility through NMDA receptor , nitric oxide , cGMP pathwayNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2004C. Y. Liu Abstract, We have reported that both glutamate and nitric oxide (NO) participated in the regulation of gallbladder motility in dorsal motor nucleus of the vagus (DMV). The aim of this study is to investigate the type of receptor in DMV that mediates the excitatory effect of glutamate on gallbladder motility and the correlation between the glutamate and NO. A frog bladder connected with a force transducer was inserted into the gallbladder to record the change of gallbladder pressure. Glutamate (65 mmol L,1, 100 nL) microinjected into DMV significantly increased the strength of gallbladder phasic contraction. This effect was abolished by ketamine (180 mmol L,1, 100 nL), the specific N -methyl- d -aspartic acid (NMDA) receptor antagonist, but was not influenced by 6-cyaon-7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX) (180 mmol L,1, 100 nL), the non-NMDA ionotropic receptor antagonist. NG -nitro- l -arginine-emthyl (l -NAME) (1 mol L,1, 100 nL), the nitric oxide synthase (NOS) inhibitor, reversed the excitatory effect of glutamate on gallbladder motility. Microinjection of sodium nitroprusside (SNP), the NO donor, into DMV enhanced the gallbladder motility, and this effect was not modulated by ketamine. Microinjection of NMDA (5 mmol L,1, 100 nL) increased the strength of gallbladder phasic contraction, and this effect was attenuated by methylene blue (100 mmol L,1, 100 nL), the soluble guanylate cyclase inhibitor. These results suggest that glutamate regulate the gallbladder motility through the NMDA receptor , NO , cGMP pathway in DMV. [source] 1,8-Cineole induces relaxation in rat and guinea-pig airway smooth muscleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009Nilberto Robson Falcão Nascimento Abstract Objectives 1,8-Cineole is a monoterpene with anti-inflammatory, vascular and intestinal smooth muscle relaxant activity. We have evaluated the potential bronchodilatatory activity of this compound. Methods 1,8-Cineole was tested against carbachol, histamine, K+ 80 mM and ovalbumin-induced bronchial contractions in Wistar rat or guinea-pig tissues. Some of the guinea-pigs had been previously sensitized with an intramuscular injection of 5% (w/v) ovalbumin/saline solution. Control animals received 0.3 ml saline. In separate experimental groups the response to 1,8-cineole (1,30 mg/kg), phenoterol (0.05,5 mg/kg) or vehicle (0.3% Tween in saline) was studied. Key findings 1,8-Cineole decreased, in vivo, rat bronchial resistance with similar efficacy as phenoterol (66.7 ± 3.2% vs 72.1 ± 5.3%). On the other hand, the maximal relaxant response to 1,8-cineole in carbachol-precontracted rat tracheas was 85.5 ± 5.7% (IC50 = 408.9 (328,5196) ,g/ml) compared with 80.2 ± 4.8% (IC50 = 5.1 (4.3,6.1) ,g/ml) with phenoterol. The addition of 1,8-cineole to guinea-pig tracheal rings tonically contracted with K+ 80 mM induced a concentration-related relaxation. The maximal relaxation elicited by 1,8-cineole was 113.6 ± 11.7% (IC50 127.0 (115.9,139.2) ,g/ml) compared with 129.7 ± 14.6% (IC50 0.13 (0.12,0.14) ,g/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8-cineole (100, 300 or 1000 ,g/ml), 15 min before inducing phasic contractions with K+ 80 mM, decreased the maximal amplitude of the contraction by 31.6 ± 4.6, 75.7 ± 2.7 and 92.2 ± 1.5%, respectively. In another set of experiments, neither the maximal response nor the IC50 for the 1,8-cineole-induced relaxation were different between normal and ovalbumin-sensitized tissues. Moreover, the relaxation of bronchial rings contracted after exposure to 1 ,g/ml ovalbumin occurred at a faster rate in rings pre-incubated with 1,8-cineole when compared with rings pre-incubated with vehicle only (Tween 0.3%). Therefore, in the first minute after the antigen challenge, the tracheal tissue relaxed after the peak contraction by 6.5, 21.4 (P < 0.05 vs control) and 66.9% (P < 0.05 vs control) in the presence of 100, 300 or 1000 ,g/ml 1,8-cineole, respectively. Conclusions 1,8-Cineole relaxed rat and guinea-pig (nonsensitized and ovalbumin-sensitized) airway smooth muscle by a nonspecific mechanism. [source] Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001B. Coulie Background: Nicotine decreases diarrhoea and pain in ulcerative colitis without reducing inflammation. Aims: (i) To evaluate the effect of ulcerative proctosigmoiditis on motor functions of an uninflamed segment of descending colon; and (ii) to assess nicotine's effects on colonic motor functions in patients and healthy subjects. Methods: In healthy subjects (n=30) and patients with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the effects of intravenous nicotine on colonic transit of solid residue by scintigraphy (healthy subjects) and on colonic motility in healthy subjects and 11 patients. Results: In ulcerative colitis, fasting colonic motility was increased, whereas motor response to a meal was significantly reduced; compliance was unchanged. In healthy subjects, high-dose nicotine induced transient high amplitude propagated contractions and relaxation of the descending colon followed by decreased phasic contractions. This dose also accelerated colonic transit. Low-dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance in healthy subjects, but did not affect motor function in ulcerative colitis. Conclusions: Ulcerative proctosigmoiditis increases fasting colonic motility and reduces tone response to a meal in the descending colon without affecting colonic compliance, suggesting changes in physiological responses but not intrinsic wall properties. Nicotine has dose-dependent effects on colonic motor activity in healthy subjects. [source] Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol IntoxicationMICROCIRCULATION, Issue 7 2010FLAVIA M. SOUZA-SMITH Please cite this paper as: Souza-Smith, Kurtz, Molina and Breslin (2010). Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication. Microcirculation17(7), 514,524. Abstract Objective:, Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods:, Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats through surgically implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results:, Lymphatics isolated from alcohol-intoxicated animals displayed significantly decreased CF compared to the dextrose group, elevated SVI versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions:, Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. [source] Effect of otilonium bromide on contractile patterns in the human sigmoid colonNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2010D. Gallego Abstract Background, The mechanism of action of the spasmolytic compound otilonium bromide (OB) on human colonic motility is not understood. The aim of our study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon. Methods, Circular sigmoid strips were studied in organ baths. Isolated smooth muscle cells from human sigmoid colon were examined using the calcium imaging technique. Key Results, Otilonium bromide inhibited by 85% spontaneous non-neural rhythmic phasic contractions (RPCs), (IC50 = 49.9 nmol L,1) and stretch-induced tone (IC50 = 10.7 nmol L,1) with maximum effects at micromolar range. OB also inhibited by 50% both on- (IC50 = 38.0 nmol L,1) and off- contractions induced by electrical stimulation of excitatory motor neurons. In contrast, the inhibitory latency period prior to off -contractions was unaffected by OB. OB inhibited acetylcholine-, substance P-, and neurokinin A-induced contractions. The L-type Ca2+ channel agonist BayK8644 reversed the effects of OB on RPCs, on- and off -contractions. Hexamethonium, atropine, the NK2 antagonist, or depletion of intracellular Ca2+ stores by thapsigargin did not prevent the inhibitory effect of OB on RPCs and electrical contractions. KCl-induced calcium transients in isolated smooth muscle cells were also inhibited by OB (IC50 = 0.2 ,mol L,1). Conclusions & Inferences, Otilonium bromide strongly inhibited the main patterns of human sigmoid motility in vitro by blocking calcium influx through L-type calcium channels on smooth muscle cells. This pharmacological profile may mediate the clinically observed effects of the drug in patients with irritable bowel syndrome. [source] The herbal preparation STW5 (lberogast®) has potent and region-specific effects on gastric motilityNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2004B. Hohenester Abstract, Functional dyspepsia (FD) is amongst the most common functional gastrointestinal disorders. Symptomatic treatment includes the use of herbal preparations whose effects on gastric motility are unclear. The present study aimed at investigating the effects of STW 5 (Iberogast®), a fixed combination of hydroethanolic herbal extracts, on gastric motility in vitro. Muscle strips from guinea-pig gastric fundus, corpus and antrum were set up in organ baths either in circular or longitudinal orientation. Addition of ethanol-free STW 5 to the organ baths (32,512 ,g mL,1) dose-dependently evoked a sustained and reversible relaxation of circular and longitudinal fundus and corpus muscle strips without changes in phasic activity. In contrast, antral muscle strips responded to STW 5 with a significant increase in the contractile force of phasic contractions without changes in tone. All effects were resistant to tetrodotoxin (0.5 ,mol L,1), atropine (1 ,mol L,1), , -conotoxin GVIA (0.5 ,mol L,1), capsaicin (1 ,mol L,1) or l -NAME (100 ,mol L,1), suggesting that neither nerves nor nitric oxide pathways were involved. These data demonstrate that STW 5 profoundly alters gastric motility in a region-specific but not layer-specific manner and thus implicates Iberogast® in the treatment of FD patients suffering from motility disorders with impaired fundus accommodation and/or antral hypomotility. [source] The urethral Kock pouch: long-term functional and oncological results in menBJU INTERNATIONAL, Issue 4 2003A.A. Shaaban The Department of Urology in Mansoura has a well-known experience in, among many things, urinary tract reconstruction in patients with bladder cancer. They review their results in 338 male patients who had a radical cystectomy and Kock pouch. They found good functional and oncological outcomes in properly selected patients. However, they also drew attention to several valve-related complications. OBJECTIVE To evaluate our experience with men who underwent radical cystectomy and urethral Kock pouch construction between January 1986 and January 1996. PATIENTS AND METHODS Complications were classified as early (within the first 3 months after surgery) or late. Continence was assessed by interviewing the patient; they were considered continent if they were completely dry with no need of protection by pads, condom catheter or medication. The patients were followed oncologically and Kaplan-Meier survival curves constructed. Urodynamic studies were used to define the possible causes of enuresis. RESULTS Three patients died after surgery from pulmonary embolism. There were 67 early complications in 63 patients. The mean (sd) follow-up was 87.8 (49.1) months. There were 111 treatment failures from cancer; of these, four men only had an isolated local recurrence in the urethra. Late complications included 72 pouch stones in 55 patients, and 36 deteriorated renal units caused by reflux (17), uretero-ileal stricture (11), nipple valve eversion (four) or stenosis (four). Interestingly, 65 renal units that were dilated before surgery improved significantly afterward. Ileo-urethral strictures occurred in seven men and anterior urethral strictures in six. Nine patients were totally incontinent and two had chronic urinary retention. Daytime continence was complete in 94% of men, with nocturnal enuresis in 55; the latter had significantly more residual urine, and a higher amplitude and duration of phasic contractions. CONCLUSIONS Orthotopic bladder substitution after cystectomy for cancer is feasible, with good functional and oncological outcomes in properly selected patients. Nevertheless, the use of a hemi-Kock pouch is associated with many valve-related complications. [source] Sympathectomy reveals ,1A - and ,1D -adrenoceptor components to contractions to noradrenaline in rat vas deferensBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2004Linda Cleary We have previously demonstrated that contractions of rat vas deferens to exogenous noradrenaline involve predominantly ,1A -adrenoceptors, but that contractions to endogenous noradrenaline involve predominantly ,1D -adrenoceptors. In this study, we have examined the effects of sympathectomy on the subtypes of ,1 -adrenoceptor in rat vas deferens in radioligand binding and functional studies. In vehicle-treated tissues, antagonist displacement of [3H]prazosin binding to ,1 -adrenoceptors was consistent with a single population of ,1 -adrenoceptors. Binding affinities for a range of ,1 -adrenoceptor antagonists were expressed as pKi values and correlated with known affinities for ,1 -adrenoceptor subtypes. The correlation was significant only with ,1A -adrenoceptors. In tissues from rats sympathectomised with 6-hydroxy-dopamine (2 × 100 mg kg,1 i.p.), binding affinity for the ,1D -adrenoceptor antagonist BMY 7378 fitted best with a two-site model. In functional studies, the potency of noradrenaline at producing total (phasic plus tonic) but not tonic contractions was increased in tissues from sympathectomised rats. Results obtained from sympathectomised rats suggest that phasic contractions are mainly ,1D -adrenoceptor mediated, whereas tonic contractions are mainly ,1A -adrenoceptor mediated, based on the effects of BMY 7378 and the ,1A -adrenoceptor antagonist RS 100329. It is concluded that the predominant ,1 -adrenoceptor in vehicle-treated rat vas deferens is the ,1A -adrenoceptor, both in terms of ligand binding and contractions to exogenous agonists. The ,1D -adrenoceptor is only detectable by ligand binding following chemical sympathectomy, but is involved in noradrenaline-evoked contractions, particularly phasic contractions, of rat vas deferens. British Journal of Pharmacology (2004) 143, 745,752. doi:10.1038/sj.bjp.0705987 [source] Characterization of the 5-hydroxytryptamine receptors mediating contraction in the pig isolated intravesical ureterBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2003Medardo Hernández This study was designed to investigate the effect of 5-hydroxytryptamine (5-HT) and to characterize the 5-HT receptors involved in 5-HT responses in the pig intravesical ureter. 5-HT (0.01,10 ,M) concentration-dependently increased the tone of intravesical ureteral strips, whereas the increases in phasic contractions were concentration-independent. The 5-HT2 receptor agonist ,-methyl 5-HT, mimicked the effect on tone whereas weak or no response was obtained with 5-CT, 8-OH-DPAT, m -chlorophenylbiguanide and RS 67333, 5-HT1, 5-HT1A, 5-HT3 and 5-HT4 receptor agonists, respectively. 5-HT did not induce relaxation of U46619-contracted ureteral preparations. Pargyline (100 ,M), a monoaminooxidase A/B activity inhibitor, produced leftward displacements of the concentration-response curves for 5-HT. 5-HT-induced tone was reduced by the 5-HT2 and 5-HT2A receptor antagonists ritanserine (0.1 ,M) and spiperone (0.2 ,M), respectively. However, 5-HT contraction was not antagonized by cyanopindolol (2 ,M), SDZ,SER 082 (1 ,M), Y-25130 (1 ,M) and GR 113808 (0.1 ,M), which are respectively, 5-HT1A/1B, 5-HT2B/2C, 5-HT3, and 5-HT4 selective receptor antagonists. Removal of the urothelium did not modify 5-HT-induced contractions. Blockade of neuronal voltage-activated sodium channels, ,-adrenergic receptors and adrenergic neurotransmission with tetrodotoxin (1 ,M), phentolamine (0.3 ,M) and guanethidine (10 ,M), respectively, reduced the contractions to 5-HT. However, physostigmine (1 ,M), atropine (0.1 ,M) and suramin (30 ,M), inhibitors of cholinesterase activity, muscarinic- and purinergic P2 -receptors, respectively, failed to modify the contractions to 5-HT. These results suggest that 5-HT increases the tone of the pig intravesical ureter through 5-HT2A receptors located at the smooth muscle. Part of the 5-HT contraction is indirectly mediated via noradrenaline release from sympathetic nerves. British Journal of Pharmacology (2003) 138, 137,144. doi:10.1038/sj.bjp.0705019 [source] | ||||||||||