Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat

2001 ◽  
Vol 280 (5) ◽  
pp. R1407-R1413 ◽  
Author(s):  
Hidehiro Kakizaki ◽  
Mitsuharu Yoshiyama ◽  
Tomohiko Koyanagi ◽  
William C. De Groat

5-Hydroxytryptamine (5-HT) receptors in the central nervous system have been implicated in the control of micturition. The present study was undertaken to evaluate the effects of a selective 5-HT1A-receptor antagonist { N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635)} on the micturition-reflex pathway in urethane-anesthetized female Wistar rats. Rhythmic isovolumetric bladder contractions evoked by bladder distension were abolished by 0.3- to 3-mg/kg iv or 30- to 100-μg intrathecal (it) administration of WAY100635 in a dose-dependent manner for periods of 3–15 min. Intrathecal injection of WAY100635 was effective only if injected at the L6-S1 spinal cord level, but not at the thoracic or cervical cord levels. WAY100635 (30–100 μg it) significantly reduced the amplitude of bladder contractions evoked by electrical stimulation of the pontine micturition center. However, the field potentials in the rostral pons evoked by electrical stimulation of pelvic nerve were not affected by intrathecal or intravenous injection of WAY100635. These results suggest that 5-HT1A receptors at the L6-S1 level of the spinal cord have an important role in the tonic control of the descending limb of the micturition-reflex pathway in the rat.

1992 ◽  
Vol 262 (3) ◽  
pp. R478-R484 ◽  
Author(s):  
M. N. Kruse ◽  
B. S. Mallory ◽  
H. Noto ◽  
J. R. Roppolo ◽  
W. C. de Groat

Micturition, which is mediated by a spinobulbospinal reflex pathway, can be modulated by various spinal and supraspinal mechanisms. This study examined modulation of the micturition reflex in decerebrate unanesthetized cats. Electrical stimulation of the pontine micturition center (PMC) elicited two types of bladder responses: small-amplitude short-duration responses due to direct activation of the bulbospinal pathway (PS-direct contractions) and large-amplitude long-duration reflex responses induced by PS-direct contractions but maintained by afferent feedback (PS-reflex contractions). Rectal and vaginal-cervical stimulation inhibited the PS-direct contractions, indicating inhibition of the descending or efferent limb of the micturition pathway. Stimulation of the central end of a transected S2 ventral root elicited recurrent inhibition of PS-reflex contractions but not of PS-direct contractions, indicating that recurrent inhibition does not directly affect the descending pathway. Continuous electrical stimulation (20 Hz) of the PMC decreased (53 +/- 21%) bladder capacity, presumably by affecting transmission in the pons or ascending input to the pons. Thus the micturition reflex could be modulated at several sites: the pons, the ascending or descending pathways, or spinal interneuronal sites.


2010 ◽  
Vol 299 (4) ◽  
pp. F785-F791 ◽  
Author(s):  
Masaru Yoshizumi ◽  
Kazumasa Matsumoto-Miyai ◽  
Akihiko Yonezawa ◽  
Masahito Kawatani

α1-Adrenergic receptor subtypes are widely distributed in the central nervous system and are involved in autonomic functions such as micturition. We investigated the presence and the role of supraspinal and/or spinal α1-adrenergic receptors in modulating the micturition reflex in conscious female Wistar rats. The expression of α1-adrenergic receptor subtypes in rat brain and lumbosacral spinal cord was studied using RT-PCR. Continuous-infusion cystometrograms were obtained in conscious rats, and α1-adrenergic receptor antagonists were administered via intracerebroventricular or intrathecal routes. The mRNA expression of α1A-, α1B-, and α1D-adrenergic receptors was detected in rat brain (midbrain and pons) and lumbosacral spinal cord (dorsal and ventral parts of spinal cord). In addition, intracerebroventricular injection of the α1-adrenergic receptor antagonist tamsulosin (1–10 μg), the selective α1A-adrenergic receptor antagonist silodosin (1–10 μg), and the selective α1D-adrenergic receptor antagonist BMY 7378 (1–10 μg) significantly prolonged the intercontraction interval (ICI) but did not alter maximum voiding pressure (MVP). Although intrathecal injection of BMY 7378 (0.0001–10 μg) did not affect ICI, tamsulosin and silodosin prolonged ICI in a dose-dependent manner. MVP was significantly reduced by intrathecal injection of tamsulosin (10 μg) but not by silodosin or BMY 7378 (0.0001–10 μg). Supraspinal α1A- and α1D-adrenergic receptors are apparently important for the regulation of reflex-bladder activity in conscious rats. Noradrenergic projection from the brain stem to the lumbosacral spinal cord may promote the afferent limb rather than the efferent limb of the micturition reflex pathway via α1A-adrenergic receptors.


2003 ◽  
Vol 90 (4) ◽  
pp. 2521-2530 ◽  
Author(s):  
C. Sévoz-Couche ◽  
M.-A. Comet ◽  
M. Hamon ◽  
R. Laguzzi

Different stressful conditions elicit a typical behavior called the defense reaction. Our aim was to determine whether 5-HT3 receptors in the nucleus tractus solitarius (NTS) are involved in 1) the inhibition of the baroreflex bradycardia and 2) the rise in blood pressure, which are known to occur during the defense reaction. In urethane-anesthetized rats, the defense reaction was elicited by electrical stimulation of the dorsomedial nucleus of the hypothalamus (DMH) or the dorsal part of the periaqueductal gray (dPAG). Direct electrical stimulation of the aortic depressor nerve was used to trigger the typical baroreflex responses. Aortic stimulation at high (100–150 μA) and low (50–90 μA) intensity produced a decrease in heart rate of –39 to –44% (relative to baseline, Group 1 responses, n = 113) and –19 to –24% ( Group 2 responses, n = 43), respectively. In spontaneously breathing rats, Group 1 and Group 2 bradycardiac responses were inhibited during DMH (–75 ± 4% and –96 ± 4%, n = 38 and n = 11, respectively), as well as dPAG (–81 ± 3% and –95 ± 4%, n = 36 and n = 10, respectively) stimulation. The aortic baroreflex bradycardia was hardly affected by DMH or dPAG stimulation when bicuculline (5 pmol), a specific GABAA receptor antagonist, had previously been microinjected into the NTS. Likewise, NTS microinjections of granisetron, a specific 5-HT3 receptor antagonist, prevented, in a dose-dependent manner, the baroreflex bradycardia inhibition. In addition, intra-NTS granisetron did not affect the rise in blood pressure induced by either site stimulation. These data show that 5-HT3 receptors in the NTS are involved in the GABAergic inhibition of the aortic baroreflex bradycardia, but not in the rise in blood pressure, occurring during the defense reaction elicited by DMH or dPAG stimulation.


2021 ◽  
Vol 22 (1) ◽  
pp. 394
Author(s):  
Simone Krueger ◽  
Alexander Riess ◽  
Anika Jonitz-Heincke ◽  
Alina Weizel ◽  
Anika Seyfarth ◽  
...  

In cell-based therapies for cartilage lesions, the main problem is still the formation of fibrous cartilage, caused by underlying de-differentiation processes ex vivo. Biophysical stimulation is a promising approach to optimize cell-based procedures and to adapt them more closely to physiological conditions. The occurrence of mechano-electrical transduction phenomena within cartilage tissue is physiological and based on streaming and diffusion potentials. The application of exogenous electric fields can be used to mimic endogenous fields and, thus, support the differentiation of chondrocytes in vitro. For this purpose, we have developed a new device for electrical stimulation of chondrocytes, which operates on the basis of capacitive coupling of alternating electric fields. The reusable and sterilizable stimulation device allows the simultaneous use of 12 cavities with independently applicable fields using only one main supply. The first parameter settings for the stimulation of human non-degenerative chondrocytes, seeded on collagen type I elastin-based scaffolds, were derived from numerical electric field simulations. Our first results suggest that applied alternating electric fields induce chondrogenic re-differentiation at the gene and especially at the protein level of human de-differentiated chondrocytes in a frequency-dependent manner. In future studies, further parameter optimizations will be performed to improve the differentiation capacity of human cartilage cells.


1981 ◽  
Vol 44 (4) ◽  
pp. 207-217 ◽  
Author(s):  
Don M. Long ◽  
Donald Erickson ◽  
James Campbell ◽  
Richard North

2001 ◽  
Vol 95 (2) ◽  
pp. 525-530 ◽  
Author(s):  
Shao-Rui Chen ◽  
Hui-Lin Pan

Background Systemic morphine is known to cause increased release of acetyicholine in the spinal cord. Intrathecal injection of the cholinergic receptor agonists or acetyicholinesterase inhibitors produces antinociception in both animals and humans. In the present study, we explored the functional importance of spinal endogenous acetylcholine in the analgesic action produced by intravenous morphine. Methods Rats were implanted with intravenous and intrathecal catheters. The antinociceptive effect of morphine was determined by the paw-withdrawal latency in response to a radiant heat stimulus after intrathecal treatment with atropine (a muscarinic receptor antagonist), mecamylamine (a nicotinic receptor antagonist), or cholinergic neurotoxins (ethylcholine mustard aziridinium ion [AF64A] and hemicholinium-3). Results Intravenous injection of 2.5 mg/kg morphine increased significantly the paw-withdrawal latency. Intrathecal pretreatment with 30 microg atropine (n = 7) or 50 microg mecamylamine (n = 6) both attenuated significantly the antinociceptive effect of morphine. The inhibitory effect of atropine on the effect of morphine was greater than that of mecamylanilne. Furthermore, the antinociceptive effect of morphine was significantly reduced in rats pretreated with intrathecal AF64A (n = 7) or hemicholinium-3 (n = 6) to inhibit the high-affinity choline transporter and acetylcholine synthesis. We found that intrathecal AF64A reduced significantly the [3H]hemicholinium-3 binding sites but did not affect its affinity in the dorsal spinal cord. Conclusions The data in the current study indicate that spinal endogenous acetylcholine plays an important role in mediating the analgesic effect of systemic morphine through both muscarinic and nicotinic receptors.


2021 ◽  
Author(s):  
S.S. Ananiev ◽  
D.A. Pavlov ◽  
R.N. Yakupov ◽  
V.A. Golodnova ◽  
M.V. Balykin

The study was conducted on 22 healthy men aged 18-23 years. The primary motor cortex innervating the lower limb was stimulated with transcranial magnetic stimulation. Using transcutaneous electrical stimulation of the spinal cord, evoked motor responses of the muscles of the lower extremities were initiated when electrodes were applied cutaneous between the spinous processes in the Th11-Th12 projection. Research protocol: Determination of the thresholds of BMO of the muscles of the lower extremities during TESCS; determination of the BMO threshold of the TA muscle in TMS; determination of the thresholds of the BMO of the muscles of the lower extremities during TESCS against the background of 80% and 90% TMS. It was found that magnetic stimulation of the motor cortex of the brain leads to an increase in the excitability of the neural structures of the lumbar thickening of the spinal cord and an improvement in neuromuscular interactions. Key words: transcranial magnetic stimulation, transcutaneous electrical stimulation of the spinal cord, neural networks, excitability, neuromuscular interactions.


Sign in / Sign up

Export Citation Format

Share Document