The effects of changing intracellular pH on calcium and potassium currents in smooth muscle cells from the guinea-pig ureter

Effect of weight training exercise and treadmill exercise on postexercise oxygen consumption. Med. Sci. Sports Exerc., Vol. 30, No. 4, pp. 518-522, 1998. To compare the effect of weight training (WT) and treadmill (TM) exercise on postexercise oxygen consumption (VO2), 15 males (mean +/- SD) age = 22.7 +/- 1.6 yr; height = 175.0 +/- 6.2 cm; mass = 82.0 +/- 14.3 kg) performed a 27-min bout of WT and a 27-min bout of TM exercise at matched rates of VO2. WT consisted of performing two circuits of eight exercises at 60% of each subject's one repetition maximum with a work/rest ratio of 45 s/60 s. Approximately 5 d after WT each subject walked or jogged on the TM at a pace that elicited an average VO2 matched with his mean value during WT. VO2 was measured continuously during exercise and the first 30 min into recovery and at 60 and 90 min into recovery. VO2 during WT (1.58 L.min-1) and TM exercise (1.55 L.min-1) were not significantly (P > 0.05) different; thus the two activities were matched for VO2. Total oxygen consumption during the first 30 min of recovery was significantly higher (P < 0.05) as a result of WT (19.0 L) compared with that during TM exercise (12.7 L). However, VO2 values at 60 (0.32 vs 0.29 L.min-1), and 90 min (0.33 vs 0.30 L.min-1) were not significantly different (P > 0.05) between WT and TM exercise, respectively. The results suggest that, during the first 30 min following exercise. WT elicits a greater elevated postexercise VO2 than TM exercise when the two activities are performed at matched VO2 and equal durations. Therefore, total energy expenditure as a consequence of WT will be underestimated if based on exercise VO2 only.     

The action of histamine on the slow-wave and spike activities of the cat and guinea pig ureter

Histamine increased the oscillation frequency of the slow-wave activity in the cat ureter and changed the characteristics of the AP plateau phase. A specific and sensitive to histamine electrogenic Na/Ca agent seems to take part in generation of the ureter spontaneous activity.     

Effects of excitatory neurotransmitters on Ca2+ channel current in smooth muscle cells isolated from guinea-pig urinary bladder

1. A whole-cell voltage clamp technique was used to examine the effects of purinoceptor and muscarinic receptor agonists on voltage-sensitive Ca2+ channels in guinea-pig isolated urinary bladder cells. 2. When the cell membrane was clamped at the holding potential, rapid application of ATP elicited a large inward current in normal solution containing 2.5 mM Ca2+, and reduced the subsequent Ca2+ channel current evoked by a depolarizing pulse (0 mV). Carbachol (CCh) elicited little membrane current, but similarly reduced the Ca2+ current. 3. When purinoceptor agonists were rapidly applied during conditioning depolarizations at +80 mV, an outward current was elicited, and the Ca2+ channel current evoked by the subsequent test potential of 0 mV was not affected. Application of CCh at +80 mV also elicited an outward current, but it reduced the subsequently evoked Ca2+ current. 4. The inhibitory effect of muscarinic agonists on the Ca2+ channel current was attenuated by caffeine (10 mM). 5. In Ca(2+)-free, low-Mg2+ solution, a Na+ current flowing through voltage-dependent Ca2+ channels was evoked by depolarization. This current was not reduced by bath application of purinoceptor agonists (ATP and alpha,beta-methylene ATP). 6. These results suggest that the main effect of purinoceptor stimulation is opening of non-selective cation channels, and that muscarinic stimulation triggers Ca2+ release from intracellular stores. Voltage-sensitive Ca2+ channels are inactivated through an increase in intracellular Ca2+ induced by either activation of purinoceptor or muscarinic receptors.     

Inhibitory action of insulin-sensitizing agents on calcium channels in smooth muscle cells from resistance arteries of guinea-pig

Herein is presented the sequence of a catfish full-length p53 cDNA obtained from a cloned B cell line cDNA library. Southern blot analyses determined that a restriction fragment linked polymorphism (RFLP) existed with PstI among outbred catfish. Western blot analyses demonstrated that, when compared to PBLs, the catfish leukocyte lines express higher levels of p53 protein. Additionally, the results of Western blot analyses and in vitro translation experiments suggest that the catfish leukocyte lines may produce truncated forms of p53 due to internal initiation.     

Effect of imipramine and ftoracizin on platelet aggregation and smooth muscle contraction of the ureter

The influence of the tricyclic antidepressants imipramine and ftoracizin on platelet aggregation and smooth muscle contractility was investigated in comparison with action of known smooth muscle relaxant and platelet aggregation inhibitor, papaverine. It has been shown that the tricyclic antidepressants possess potent spasmolytic activity but unlike papaverine have no effect on platelet aggregation. The biochemical mechanisms of the non-specific action of tricyclic antidepressants as well as some other structurally related-drugs are discussed.     

The action of adrenergic substances on the smooth muscle of the rat trachea

Adrenalin and noradrenaline first induced an increase in the trachea smooth muscle response with its subsequent decline in rats. Phentolamine decreases the muscle responses in its thoracic part and practically does not affect it in the cervical segments. The adrenergic neural fibres seem to terminate at the smooth muscle cells and the neurons of intramural ganglia.     

The influence of post-mortem conditions on contractile and relaxant responsiveness of guinea-pig isolated tracheal smooth muscle

Responsiveness to various contractile and relaxant agonists was assessed in tracheal preparations from guinea-pigs that had been incubated in situ at 4-37 degrees C for 0-168 h post-mortem. The potencies of histamine and acetylcholine were increased up to 168 h at 4 degrees C post-mortem and up to 24 h post-mortem at 22 degrees C. Histamine potency also increased with increasing post-mortem time at 37 degrees C. After 48 h at 22 degrees C and 8 h at 37 degrees C, responses to all spasmogens were abolished. Increases in histamine and acetylcholine potencies were similarly observed in tracheal tissue that had been removed at death and then incubated at 4 degrees C in oxygenated Krebs-bicarbonate solution for 0-168 h. The increased potency of these drugs may be explained by epithelial damage and/or loss of an epithelium-derived inhibitory factor (EpDIF). Both basal and spasmogen-stimulated increases in intracellular phosphoinositides fell with increasing time and ambient temperature post-mortem, despite the fact that contraction in response to these agonists could still be evoked. This suggests the selective failure of this signal transduction pathway and the maintenance of responsiveness via other mechanisms. The potencies and maximum effects of relaxant agonists remained unaltered in tracheal tissue with increasing time post-mortem, suggesting little change in the function of the appropriate receptor-signal transduction processes. This study has therefore demonstrated that at 4 degrees C. contractile and relaxant responses were preserved for up to 168 h post-mortem, although the modulatory influence of the epithelium on histamine and acetylcholine responses was rapidly lost.     

Characterization of action potential-triggered [Ca2+]i transients in single smooth muscle cells of guinea-pig ileum

Cytology can be a rewarding diagnostic technique in equine practice. The respiratory tract readily lends itself to sampling for cytologic evaluation from the upper to lower regions of the system. This article discusses preservation and staining techniques that will allow the practitioner to present satisfactory samples to the laboratory. General considerations for cytologic analysis are discussed as well as the specific findings for individual disorders of the respiratory tract. The proper use of cytologic findings in conjunction with other diagnostic techniques for the respiratory tract are also discussed.     

The action of toxins derived from scorpion venom on the ileal smooth muscle preparation

The properties of the 37400 oncogenic strain of Agrobacterium tumefaciens are described. This strain was derived from the VI lysogenic strain originally isolated by Hamilton from a Zinnia elegans tumour. Strain 37400 has a number of properties which render it suitable for quantitative and genetic studies. It is cured of prophages and can serve as a universal sensitive indicator for a number of phages isolated from various lysogenic strains of Agrobacterium tumefaciens. Its good growth properties in synthetic media and at elevated temperatues enable the isolation of auxotrophic mutants and temperature sensitive phage mutants. Preliminary experiments show that strain 37400 will serve as suitable starting material for conjugation experiments under defined conditions.     

Measurement of intercellular electrical coupling in guinea-pig detrusor smooth muscle

Ropivacaine, a new long-acting local anesthetic, is currently being investigated for the treatment of ulcerative colitis. In view of the increased incidence of dysplasia and neoplasia associated with ulcerative colitis, it is important that the medical treatment of these patients does not stimulate cell proliferation further. This study was performed to evaluate the effect of ropivacaine on the proliferation of human colon adenocarcinoma cells (HT-29 and Caco-2) in vitro. A serum-induced proliferation assay of human colon adenocarcinoma cells was used. Ropivacaine inhibited the growth of HT-29 and Caco-2 cells in a dose-dependent manner. Fifty percent inhibition of growth was found at a ropivacaine concentration of 250 microM when the HT-29 cells were cultured in 1% fetal calf serum and of 550 microM when the HT-29 cells were cultured in 10% serum. The effective concentrations are within the range of the therapeutic concentrations obtained in the colon of patients treated rectally with ropivacaine. Lidocaine, hydrocortisone, and 5-aminosalicylic acid were found to be less potent than ropivacaine in inhibiting proliferation. Ropivacaine caused a dose-dependent membrane depolarization that appeared to correlate with the inhibited cell proliferation, whereas the effect was not related to inhibition of leukotriene B4 or prostaglandin E2. In conclusion, the antiproliferative activity of ropivacaine, combined with previously reported anti-inflammatory activities, makes this drug an interesting new alternative for the local treatment of ulcerative colitis.     

Pharmacology of neurotransmission to the smooth muscle of the rat and the guinea-pig prostate glands

The advantages of customized Laboratory Information Management's Systems (LIMS) are their focus on the special aspects of their users' needs. Differences in the research and development or production chain in the individual organizations lead to an increase of interest in customized systems. Usually, also for customized systems, the core software is commercially available. The individual application modules as the Customized part of the LIMS are the most critical elements within the validation process. The topic of this paper is to give an example of the validation of a customized analytical LIMS. Validation of complex computerized systems guarantees the intended use and is therefore an unavoidable requirement of authorities. The audit of the supplier of the individual programmed modules, the user requirement specifications and the acceptance testing and results, respectively, on the software are of special interest within a customized LIMS. The hardware suitability and the principal processing routines are also a very important part of the whole validation process, but they will not be discussed in detail in this paper.     

Muscarinic receptor subtypes controlling the cationic current in guinea-pig ileal smooth muscle

1. The effects of muscarinic antagonists on cationic current evoked by activating muscarinic receptors with the stable agonist carbachol were studied by use of patch-clamp recording techniques in guinea-pig single ileal smooth muscle cells. 2. Ascending concentrations of carbachol (3-300 microM) activated the cationic conductance in a concentration-dependent manner with conductance at a maximally effective carbachol concentration (Gmax) of 27.4+/-1.4 nS and a mean -log EC50 of 5.12+/-0.03 (mean+/-s.e.mean) (n=114). 3. Muscarinic antagonists with higher affinity for the M2 receptor, methoctramine, himbacine and tripitramine, produced a parallel shift of the carbachol concentration-effect curve to the right in a concentration-dependent manner with pA2 values of 8.1, 8.0 and 9.1, respectively. 4. All M3 selective muscarinic antagonists tested, 4-DAMP, p-F-HHSiD and zamifenacin, reduced the maximal response in a concentration-dependent and non-competitive manner. This effect could be observed even at concentrations which did not produce any increase in the EC50 for carbachol. At higher concentrations M3 antagonists shifted the agonist curve to the right, increasing the EC50, and depressed the maximum conductance response. Atropine, a non-selective antagonist, produced both reduction in Gmax (M3 effect) and significant increase in the EC50 (M2 effect) in the same concentration range. 5. The depression of the conductance by 4-DAMP, zamifenacin and atropine could not be explained by channel block as cationic current evoked by adding GTPgammaS to the pipette (without application of carbachol) was unaffected. 6. The results support the hypothesis that carbachol activates M2 muscarinic receptors so initiating the opening of cationic channels which cause depolarization; this effect is potentiated by an unknown mechanism when carbachol activates M3 receptors. As an increasing fraction of M3 receptors are blocked by an antagonist, the effects on cationic current of an increasing proportion of activated M2 receptors are disabled.     

Role of intracellular Ca2+ in the K channel opener action of CGRP in the guinea-pig ureter

1. The aim of this study was to assess the role of sarcoplasmic reticulum (SR) calcium (Ca2+) in the smooth muscle relaxant and hyperpolarizing actions of calcitonin gene-related peptide (CGRP) in the guinea-pig ureter. 2. CGRP (0.1 microM) rapidly and transiently reduced myogenic phasic contractions (twitches) produced by electrical field stimulation (EFS). Approximately 70% of the response to CGRP was antagonized by glibenclamide (1 microM). 3. Cyclopiazonic acid (CPA, 10 microM), ryanodine (100 microM) and thapsigargin (1 microM) reduced only the glibenclamide-sensitive component of the response to CGRP (0.1 microM) but did not modify the mechano-inhibitory effect of cromakalim (3 microM). A low concentration of CPA (1 microM), assumed to produce a limited impairment of Ca2+ uptake from the stores, prolonged the duration of the inhibitory response to CGRP. Pre-exposure to caffeine (5 mM) inhibited the suppression of twitches by CGRP or cromakalim. 4. When the frequency of EFS was increased, the suppression of twitches by CGRP was reduced. Under these conditions, CPA (1 microM) again prolonged the duration of the inhibitory response to CGRP. 5. CGRP (0.1 microM) and cromakalim (3 microM) markedly depressed the phasic component of contractions to 80 mM KCl. CPA (10 microM) antagonized the inhibitory effect of CGRP but not that of cromakalim. Inhibition of the tonic contraction to 80 mM KCl by CGRP was insensitive to CPA. 6. In sucrose gap experiments, a 5 min exposure to CGRP (0.1 microM) or cromakalim (3 microM) produced a sustained membrane hyperpolarization. Caffeine (5 mM) produced a glibenclamide-sensitive transient hyperpolarization followed by a sustained depolarization. When tested in a Ca(2+)-free medium the hyperpolarization produced by CGRP, cromakalim or caffeine was reduced. In normal Krebs, pre-exposure to CPA (10 microM, 60 min) only abolished the hyperpolarization induced by CGRP. In contrast, 5 min after a caffeine challenge (5 mM) the hyperpolarizations induced by CGRP or cromakalim were reduced. The CGRP-induced hyperpolarization was insensitive to apamin (0.1 microM) or charybdotoxin (0.1 microM). 7. We conclude that the K channel-opening action of CGRP in the guinea-pig ureter requires the mobilization of intracellular Ca2+ from a caffeine- and CPA-sensitive store, leading to transient activation of glibenclamide-sensitive K channels. The K channel-opening action of caffeine appears to involve Ca2+ mobilization from a store which is insensitive to depletion by CPA.     

血管平滑肌细胞的增殖因素及机制

血管平滑肌细胞(VSMC)增殖已成为目前心血管疾病研究领域里的热点,VSMC增殖、迁移及凋亡在冠状动脉粥样硬化(AS)、冠状动脉搭桥术、经皮冠状动脉介入治疗(PCI)术后血管再狭窄的发生和发展过程中起重要作用.本文作者对VSMC增殖及促增殖因素和机制进行综述.     

The mechanism of stressor suppression of the contractile function and reactivity of aortic smooth muscle

Blockade of the NO synthesis did not change the stressor augmentation of the acetylcholine-induced endothelium-dependent relaxation. The immobilisation stress seems to suppress the contractile function and the reactivity of the aorta smooth muscle reactivity as the result of augmentation of the NO basal production in endotheliocytes.     

Effects of dachengqi decoction and rhubarb on cellular electrical activities in smooth muscle of the guinea-pig taenia coli

The effects of Dachengqi decoction (DCQ) and Rhubarb (Rb) on spontaneous cellular electrical activities of guinea-pig's taenia coli has been studied by intracellular microelectrode technique. DCQ and Rb could both improve depolarization of cell membrane, speed up the burst of slow wave potential (when drug concentration was 1%, P > 0.05; 10% or 20%, P < 0.05), which was dose dependent. At the same concentration, the effects of Rb were more significant than that of DCQ. These results suggested that DCQ and Rb enhanced directly the cellular electrical excitability so as to strengthen the contraction of colon, is one of the mechanisms of these drugs in cellular level on diarrhea action. The ionic basis of the effects might be that DCQ and Rb reduced the K+conductance of cell membrane in rest state.     

The release of a coronary vasodilator metabolite from the guinea-pig isolated perfused heart stimulated by catecholamines, histamine and electrical pacing and by exposure to anoxia

The results of surveys and inquiries to identify autistic children, carried out in England and Wales, the U.S.A. and Denmark, are compared. Three studies, in each of which either a total population of children or a wide range of handicapped children was screened, using case-note inspection and interviews, all estimated the prevalence of the autistic syndrome to be between four and five children per 10,000 aged under 15 years. Inquiries that counted diagnosed cases only or that relied upon local authority records produced much lower prevalence rates for the autistic syndrome. The reasons for this are examined, and the implications for prevalence studies of handicapping conditions are discussed.     

Potentiation of bradykinin action on smooth muscle by a scorpion venom extract

Gel filtration of the water extract of the venom of the scorpion T. serrulatus showed four peaks; the first peak (P1) is devoid of toxic activity but increases the bradykinin-induced contraction of isolated rat uterus and guinea-pig ileum. The stepwise fractionation of the pooled P1 peak was performed in a DEAE-cellulose column and the bradykinin potentiating activity was found in the second protein peak. Finger-printing of this material showed that the bradykinin potentiating material migrates to the anode, giving two spots when submitted to chromatography, the activity being found in the spot that presents the greatest Rf. The potentiator is destroyed by heating at 97 degrees C, is not dialysable and is destroyed by incubation with pronase. Some of these properties differentiate it from the BPF's from snake venoms.