Comparative Effects of Intravesical Versus Extravesical Administration of ZD6169 and Cromakalim on the Response of the In Vitro Rat Whole Bladder to Field Stimulation

1998 ◽  
Vol 159 (6) ◽  
pp. 2263-2264
Author(s):  
A. Chun ◽  
D.L. Bertelsen ◽  
J. Murphy ◽  
S. Kau ◽  
R.M. Levin
Keyword(s):  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Felipe P. Perez ◽  
Bryan Maloney ◽  
Nipun Chopra ◽  
Jorge J. Morisaki ◽  
Debomoy K. Lahiri

AbstractLate Onset Alzheimer’s Disease is the most common cause of dementia, characterized by extracellular deposition of plaques primarily of amyloid-β (Aβ) peptide and tangles primarily of hyperphosphorylated tau protein. We present data to suggest a noninvasive strategy to decrease potentially toxic Aβ levels, using repeated electromagnetic field stimulation (REMFS) in primary human brain (PHB) cultures. We examined effects of REMFS on Aβ levels (Aβ40 and Aβ42, that are 40 or 42 amino acid residues in length, respectively) in PHB cultures at different frequencies, powers, and specific absorption rates (SAR). PHB cultures at day in vitro 7 (DIV7) treated with 64 MHz, and 1 hour daily for 14 days (DIV 21) had significantly reduced levels of secreted Aβ40 (p = 001) and Aβ42 (p = 0.029) peptides, compared to untreated cultures. PHB cultures (DIV7) treated at 64 MHz, for 1 or 2 hour during 14 days also produced significantly lower Aβ levels. PHB cultures (DIV28) treated with 64 MHz 1 hour/day during 4 or 8 days produced a similar significant reduction in Aβ40 levels. 0.4 W/kg was the minimum SAR required to produce a biological effect. Exposure did not result in cellular toxicity nor significant changes in secreted Aβ precursor protein-α (sAPPα) levels, suggesting the decrease in Aβ did not likely result from redirection toward the α-secretase pathway. EMF frequency and power used in our work is utilized in human magnetic resonance imaging (MRI, thus suggesting REMFS can be further developed in clinical settings to modulate Aβ deposition.


1980 ◽  
Vol 238 (2) ◽  
pp. E157-E166 ◽  
Author(s):  
M. J. Harper ◽  
L. W. Coons ◽  
D. A. Radicke ◽  
B. J. Hodgson ◽  
G. Valenzuela

Contractile activity of the ampulla of rabbit oviducts removed 24 h after an ovulating injection was studied in vitro. Spontaneous activity, field-stimulated activity, and response to phenylephrine were studied in normal, reversed, and scraped (endosalpinx removed) sections of tissues in the presence or absence of inhibitors of prostaglandin synthetase (8 or 51 micrograms/ml indomethacin or 10 or 100 micrograms/ml 5,8,11,14-eicosatetraynoic acid (ETA)). The effects of in vivo treatment with 10 mg/kg of indomethacin on the same responses were examined. Scraped tissues produced more prostaglandin E and F (measured by radioimmunoassay) than did normal tissues, and this production was suppressed by 10 micrograms/ml of indomethacin or 100 micrograms/ml of ETA. Production of prostaglandin by normal tissues was not depressed by these compounds in vitro, but was significantly reduced by pretreatment of the animals with indomethacin in vivo. In the absence of the endosalpinx, the myosalpinx exhibited spontaneous activity and responded to field stimulation and phenylephrine. Scraped and reversed tissues, however, showed a faster decline in response to field stimulation than normal tissues, and this was due to the traumatization. By contrast, traumatization increased the sensitivity of the tissue to respond to phenylephrine. Inhibition of prostaglandin synthetase by low doses of indomethacin or ETA prevented desensitization of the tissue to field stimulation, but this desensitization was little affected by the higher doses of indomethacin in vitro or in vivo. ETA did not affect the phenylephrine dose-response curves and nor did 8 micrograms/ml of indomethacin, whereas the high dose was inhibitory. Spontaneous activity was only affected by the in vivo pretreatment with indomethacin, which prevented the decline in activity of scraped tissue with time.


1998 ◽  
Vol 274 (2) ◽  
pp. L220-L225 ◽  
Author(s):  
I. McGrogan ◽  
L. J. Janssen ◽  
J. Wattie ◽  
P. M. O’Byrne ◽  
E. E. Daniel

To investigate the role of prostaglandin (PG) E2 in allergen-induced hyperresponsiveness, dogs inhaled either the allergen Ascaris suum or vehicle (Sham). Twenty-four hours after inhalation, some animals exposed to allergen demonstrated an increased responsiveness to acetylcholine challenge in vivo (Hyp-Resp), whereas others did not (Non-Resp). Strips of tracheal smooth muscle, either epithelium intact or epithelium denuded, were suspended on stimulating electrodes, and a concentration-response curve to carbachol (10−9 to 10−5 M) was generated. Tissues received electrical field stimulation, and organ bath fluid was collected to determine PGE2content. With the epithelium present, all three groups contracted similarly to 10−5 M carbachol, whereas epithelium-denuded tissues from animals that inhaled allergen contracted more than tissues from Sham dogs. In response to electrical field stimulation, Hyp-Resp tissues contracted less than Sham tissues in the presence of epithelium and more than Sham tissues in the absence of epithelium. PGE2release in the muscle bath was greater in Non-Resp tissues than in Sham or Hyp-Resp tissues when the epithelium was present. Removal of the epithelium greatly inhibited PGE2release. We conclude that tracheal smooth muscle is hyperresponsive in vitro after in vivo allergen exposure only when the modulatory effect of the epithelium, largely through PGE2 release, is removed.


1976 ◽  
Vol 41 (5) ◽  
pp. 764-771 ◽  
Author(s):  
J. Richardson ◽  
J. Beland

Human airways, from the middle of the trachea to the distal bronchi, were studied in vitro for the presence of inhibitory nerves. The tissue was obtained from operations and from recent autopsies. Electrical field stimulation of the tissues demonstrated cholinergic, excitatory nerves and their effect was blocked by atropine. Field stimulation of the tissues, in the presence of atropine, relaxed the smooth muscle even when the muscle was contracted by histamine. The field stimulation-induced relaxation was neither blocked nor modified by adrenergic blocking agents. Maximum relaxation of the bronchial muscle was obtained with a pulse duration of 1–2 ms, 70 V,and frequencies of 20 Hz and greater. The tracheal smooth muscle showed 85%of maximal relaxation with a frequency of 10 Hz. Tetrodotoxin, blocked the field stimulation-induced relaxation for pulse durations of 2 ms; this indicated that nerves were being stimulated. The airway system shows some of the characteristics of the nonadrenergic inhibitory system in the gastrointestinal tract and of the system reported in the guinea pig trachealis muscle.No evidence of adrenergic inhibitory fibers was found in the bronchial muscle with either pharmacological or histochemical techniques. These findings suggest that the nonadrenergic inhibitory system is the principal inhibitory system for the smooth muscle of human airways. We suggest that a defect in the airway system, such as that shown in the gastrointestinal tract, may be an explanation for the hyperreactive airways of asthma and chronic bronchitis.


1980 ◽  
Vol 238 (1) ◽  
pp. C27-C33 ◽  
Author(s):  
M. S. Kannan ◽  
E. E. Daniel

The structural bases for myogenic and neurogenic control of canine tracheal smooth muscle were studied. At optimum lengths, strips of muscle showed insignificant neurogenic or myogenic tone. Atropine and/or tetrodotoxin blocked the contractile responses elicited on electrical field stimulation of intrinsic nerves. After raising the tone with tetraethylammonium ion and in the presence of atropine, field stimulation of nerves caused a relaxation, a major component of which was blocked by propranolol and/or tetrodotoxin, suggesting an effect mediated through interaction of mediator released from sympathetic nerves with beta-adrenergic receptors. Electron microscopic studies revealed gap junctions between extensions of smooth-muscle cells and a sparse innervation. The axonal varicosities, corresponding to cholinergic (predominantly) and adrenergic (occasionally) nerves, were seen predominantly in the clefts between cell bundles. The physiological responses were compared with the morphological features. Although this muscle exhibits multiunit behavior in vitro, implying that nerves initiate the coordinate activity, its ultrastructural features suggest a potential for single-unit behavior.


1988 ◽  
Vol 65 (1) ◽  
pp. 57-64 ◽  
Author(s):  
G. L. Jones ◽  
P. M. O'Byrne ◽  
M. Pashley ◽  
R. Serio ◽  
J. Jury ◽  
...  

Airway hyperresponsiveness occurs after inhalation of O3 in dogs. The purpose of this study was to examine the responsiveness of trachealis smooth muscle in vitro to electrical field stimulation, exogenous acetylcholine, and potassium chloride from dogs with airway hyperresponsiveness after inhaled O3 in vivo and to compare this with the responsiveness of trachealis muscle from control dogs. In addition, excitatory junction potentials were measured with the use of single and double sucrose gap techniques in both groups of dogs to determine whether inhaled O3 affects the release of acetylcholine from parasympathetic nerves in trachealis muscle. Airway hyperresponsiveness developed in all dogs after inhaled O3 (3 ppm for 30 min). The acetylcholine provocative concentration decreased from 4.11 mg/ml before O3 inhalation to 0.66 mg/ml after O3 (P less than 0.0001). The acetylcholine provocative concentration increased slightly after control inhalation of dry room air. Airway smooth muscle showed increased responses to both electrical field stimulation and exogenous acetylcholine but not to potassium chloride in preparations from dogs with airway hyperresponsiveness in vivo. The increased response to electrical field stimulation was not associated with a change in excitatory junctional potentials. These results suggest that a postjunctional alteration in trachealis muscle function occurs after inhaled O3 in dogs, which may account for airway hyperresponsiveness after O3 in vivo.


1992 ◽  
Vol 262 (4) ◽  
pp. G695-G702 ◽  
Author(s):  
H. D. Allescher ◽  
G. Tougas ◽  
P. Vergara ◽  
S. Lu ◽  
E. E. Daniel

Antropyloroduodenal motility was recorded in seven anesthetized dogs to assess the role of nitric oxide and L-arginine metabolites in nonadrenergic noncholinergic (NANC) mediation of pyloric relaxation. Pyloric activity induced by duodenal field stimulation was inhibited by antral field stimulation and electrical vagal stimulation. Intra-arterial NG-L-arginine-methyl-ester (L-NAME) reduced the inhibition from antral or vagal stimulation (P less than 0.05). Intravenous infusion of L-NAME also blocked the inhibitory effect of vagal and antral stimulation but left the tetrodotoxin-insensitive action of intra-arterial vasoactive intestinal peptide (VIP) and sodium nitroprusside unchanged. L-Arginine reversed the effect of L-NAME whereas D-arginine did not. L-NAME enhanced pyloric contractions to intra-arterial acetylcholine. The NANC inhibition of the substance P-stimulated pyloric response in vitro was blocked by L-NAME and reversed by addition of L-arginine. Sodium nitroprusside was effective as a relaxant in vitro but VIP was not. These data suggest that metabolites of L-arginine mediate neural inhibition of canine pyloric motor activity.


1987 ◽  
Vol 72 (2) ◽  
pp. 233-238 ◽  
Author(s):  
Stephen T. Green

1. The role of the autonomic nervous system in the control of thyroxine release from the rat thyroid gland in vitro, has been investigated using electrical field stimulation as a device to induce intrathyroidal nerves to release their neurotransmitters. 2. The effects of field stimulation on follicular cell membrane potential and input resistance have been investigated using continuous intracellular recordings from individual cells. 3. Electrical field stimulation promotes up to an eightfold increase in throxine release from the thyroid gland in vitro. This effect is blocked by the neurotoxin, tetrodotoxin. 4. Electrical field stimulation has no effect on follicular cell membrane potential or input resistance. This is consistent with the results of previous pharmacological experiments using this preparation. 5. It is concluded that electrical field stimulation induces intrathyroidal nerves to release their neurotransmitters, and that the net effect of this is to cause thyroxine release from the thyroid follicles. The existence of a directly acting secretomotor innervation to the thyroid follicle is suggested.


2014 ◽  
Vol 225 ◽  
pp. 90-96 ◽  
Author(s):  
Roger D. Madison ◽  
Grant A. Robinson ◽  
Christian Krarup ◽  
Mihai Moldovan ◽  
Qiang Li ◽  
...  

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