Effect of different 5‐hydroxytryptamine receptor subtype antagonists on the micturition reflex in rats

Testa, Rodolfo; Guarneri, L.; Angelico, Patrizia; Velasco, Cristina; Poggesi, Elena; Cilia, Antonio; Leonardi, Amedeo

doi:10.1046/j.1464-410x.2001.02038.x

Cited by 73 publications

(125 citation statements)

References 28 publications

Supporting

Mentioning

116

Contrasting

Order By: Relevance

“…5-HT immunoreactivity has also been associated with bladder recovery (Wrathall and Emch, 2006). Administration of 5-HT agonists facilitates the voiding reflex (Lecci et al, 1992), whereas 5-HT antagonists increase bladder capacity and inhibits the voiding reflex (Testa et al, 1999). The higher numbers of 5-HT-IR fibers in treated rats may thus help explain the drug-induced improvement of bladder function.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury

Erschbamer¹,

Pernold²,

Olson³

2007

Journal of Neuroscience

110

104

View full text Add to dashboard Cite

Lack of axon regeneration in the adult CNS has been attributed partly to myelin inhibitors and the properties of astrocytes. After spinal cord injury, proliferating astrocytes not only represent a physical barrier to regenerating axons but also express and secrete molecules that inhibit nerve growth, including chondroitin sulfate proteoglycans (CSPGs). Epidermal growth factor receptor (EGFR) activation triggers astrocytes into becoming reactive astrocytes, and EGFR ligands stimulate the secretion of CSPGs as well as the formation of cribriform astrocyte arrangements that contribute to the formation of glial scars. Recently, it was shown that EGFR inhibitors promote nerve regeneration in vitro and in vivo. Blocking a novel Nogo receptor interacting mechanism and/or effects of EGFR inhibition on astrocytes may underlie these effects. Here we show that rats subjected to weight-drop spinal cord injury can be effectively treated by direct delivery of a potent EGFR inhibitor to the injured area, leading to significantly better functional and structural outcome. Motor and sensory functions are improved and bladder function is restored. The robust effects and the fact that other EGFR inhibitors are in clinical use in cancer treatments make these drugs particularly attractive candidates for clinical trials in spinal cord injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury

Erschbamer¹,

Pernold²,

Olson³

2007

Journal of Neuroscience

110

104

View full text Add to dashboard Cite

show abstract

“…Compounds targeting the bladder afferent pathway often produce this effect (6,7,17,40). "Shutdown" of bladder rhythmic contraction reflects an increased threshold for induction of contractions and an increased bladder capacity in the conscious cystometrographic study (17).…”

Section: Discussionmentioning

confidence: 99%

An excitatory role for peripheral EP₃ receptors in bladder afferent function

Su¹,

Lashinger²,

Leon³

et al. 2008

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The excitatory roles of EP3 receptors at the peripheral afferent nerve innervating the rat urinary bladder have been evaluated by using the selective EP3 antagonist (2E)-3-{1-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-1H-indol-7-yl}-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041). The bladder rhythmic contraction model and a bladder pain model measuring the visceromotor reflex (VMR) to urinary bladder distension (UBD) have been used to evaluate DG-041 in female rats. In addition, male rats [spontaneously hypertensive rat (SHR), WistarKyoto (WKY), and Sprague-Dawley (SD)] were anesthetized with pentobarbital sodium, and primary afferent fibers in the L 6 dorsal root were isolated for recording the inhibitory response to UBD following intravenous injection of DG-041. Intravenous injection of DG-041 (10 mg/kg), a peripherally restricted EP 3 receptor antagonist, significantly reduced the frequency of bladder rhythmic contraction and inhibited the VMR response to bladder distension. The magnitude of reduction of the VMR response was not different in the different strains of rats (SD, SHR, and WKY). Furthermore, quantitative characterization of the mechanosensitive properties of bladder afferent nerves in SHR, WKY, and SD rats did not show the SHR to be supersensitive to bladder distension. DG-041 selectively attenuated responses of mechanosensitive afferent nerves to UBD, with strong suppression on the slow-conducting, high-threshold afferent fibers, with equivalent activity in the three strains. We conclude that sensitization of afferent nerve activity was not one of the mechanisms of bladder hypersensitivity in SHR. EP 3 receptors are involved in the regulation of bladder micturition and bladder nociception at the peripheral level.EP3; viscermotor reflex; bladder rhythmic contraction; bladder distension; afferent nerve SENSATION ASSOCIATED WITH the urinary bladder is conveyed primarily by pelvic and hypogastric nerves, by which the signal is relayed to the central nervous system (CNS). Most afferent fibers innervating the musculature of the bladder body pass through the pelvic nerve, whereas the majority of afferent endings in the bladder submucosa are derived from the hypogastric nerve (41), suggesting that the afferent fibers in the pelvic and hypogastric nerves have different roles, signaling mechanical stimulation (e.g., bladder distension) and chemical stimulation (e.g., inflammation), respectively (20,22,30,34). Bladder distension is a natural mechanical stimulus to evoke sensations such as fullness, urgency, and pain while the literature suggests a complex regulatory role of prostaglandins (PGs) in multiple aspects of urinary bladder physiology/pathophysiology. PGE 2 , one of the principal PGs, is synthesized in urothelium and detrusor smooth muscle (19,24,25,27) as well as in neurons and glial cells (18,23) and is released in response to various physiological (e.g., bladder distension) and pathological (e.g., mediators of inflammation) stimulation. PGE 2 interacts with four EP receptor subt...

show abstract

“…Thus we did not detect any drug effects of WAY-100635 interacted with 8-OH-DPAT treatment in the present study. Some studies have reported that rhythmic isovolumetric bladder contractions in rats are inhibited by the iv administration of WAY-100635 in a dosedependent manner with a short recovery time of Ͻ20 min (19,31). However, those isovolumetric IVP results have not been based on an examination of the effects of drugs on EUS activity.…”

Section: Effects Of 8-oh-dpat (03 Mg/kg Iv) and Way-100635 (01 Mg/kmentioning

confidence: 99%

“…However, contradictory results have led to various interpretations of these receptor subtype functions in different animal species. Because the rat model has recently been widely used as the main species model for investigating LUT functions, the effects of a 5-HT 1A receptor agonist on LUT functions have been extensively investigated in rats (4,7,11,14,17,19,31).…”

mentioning

confidence: 99%

Does pharmacological activation of 5-HT_1A receptors improve urine flow rate in female rats?

Chen

Hsieh

Fan

et al. 2016

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Chen SC, Hsieh TH, Fan WJ, Lai CH, Peng CW. Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats? Am J Physiol Renal Physiol 311: F166 -F175, 2016. First published May 4, 2016 doi:10.1152/ajprenal.00469.2015.-The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincterelectromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after a neuromuscular blockade (NMB) treatment and bilateral hypogastric nerve transection. Our results revealed that 8-OH-DPAT significantly increased the maximal UFR but reduced the mean UFR. This discrepancy may be because 8-OH-DPAT markedly increased the maximal UFR during the initial segment of the flow duration and subsequently induced an approximately zero level of long oscillatory waves during the remaining flow duration. Thus the mean UFR was reduced because of the prolonged approximately zero level of the UFR. However, paralyzing the EUS with an NMB agent, 8-OH-DPAT, significantly increased the maximal and mean UFRs because the prolonged zero level of the oscillatory UFR did not continue. These results support the hypothesis that the increased UFR in female rats during voiding is due to the induction of urethral smooth muscle relaxation by 8-OH-DPAT. This paper provides a detailed understanding of the role of 5-HT 1A receptors in controlling the UFR in female rats. intravesical pressure; EUS-EMG; 8-OH-DPAT; WAY-100635; neuromuscular blockade THE PRIMARY FUNCTIONS OF THE lower urinary tract (LUT) are storage and periodic urine elimination. These functions require reciprocal coordination between the urinary bladder and urethra outlets, including the bladder neck, urethra, and external urethral sphincter (EUS). The urethra consists of smooth and striated muscle layers that are regulated by the following three peripheral nerve sets: sacral parasympathetic (pelvic nerves) and thoracolumbar sympathetic nerves (hypogastric nerves) that innervate urethral smooth muscles, and sacral somatic nerves (pudendal nerves) that innervate urethral striated muscles including the EUS and pelvic floor muscles.Receptors for serotonin [5-hydroxytryptamine (5-HT)] comprise 14 structurally different 5-HT receptors in mammalian species, including 7 subfamilies (5-HT 1 -5-HT 7 ) (28). Pharmacological studies in animals have indicated that the three sets of LUT nerve terminals contain numerous 5-HT receptor subfamilies. Specifically, 5-HT 1A receptors are vital to LUT functions (32). The effects of 5-HT...

show abstract

Effect of different 5‐hydroxytryptamine receptor subtype antagonists on the micturition reflex in rats

Abstract: These findings confirm that only selective 5-HT1A receptor antagonists have favourable effects on the bladder, inducing an increase in bladder capacity with no derangement of bladder contractility.

Cited by 73 publications

References 28 publications

Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury

Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury

An excitatory role for peripheral EP₃ receptors in bladder afferent function

Does pharmacological activation of 5-HT_1A receptors improve urine flow rate in female rats?

Contact Info

Product

Resources

About

Effect of different 5‐hydroxytryptamine receptor subtype antagonists on the micturition reflex in rats

Abstract: These findings confirm that only selective 5-HT1A receptor antagonists have favourable effects on the bladder, inducing an increase in bladder capacity with no derangement of bladder contractility.

Cited by 73 publications

References 28 publications

Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury

Inhibiting Epidermal Growth Factor Receptor Improves Structural, Locomotor, Sensory, and Bladder Recovery from Experimental Spinal Cord Injury

An excitatory role for peripheral EP3 receptors in bladder afferent function

Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats?

Contact Info

Product

Resources

About

An excitatory role for peripheral EP₃ receptors in bladder afferent function

Does pharmacological activation of 5-HT_1A receptors improve urine flow rate in female rats?