Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

Matsumoto, Yoshihiro; Miyazato, Minoru; Yokoyama, Hitoshi; Kita, Masafumi; Hirao, Yoshihiko; Chancellor, Michael B.; Yoshimura, Naoki

doi:10.1016/j.urology.2012.01.022

Cited by 25 publications

(30 citation statements)

References 29 publications

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“…This was instituted after previous NHANES installments demonstrated significant deficiencies within the U.S. population and it was discovered that folic acid supplementation could help prevent neural tube defects. (2, 4) Since that time, there have been multiple studies that have shown significant increases in overall serum folate concentrations. (2, 5, 15) To our knowledge, this is the first study that specifically examines the relationship between serum folate and varying levels of DFE intake over the spectrum of ages in United States males.…”

Section: Discussionmentioning

confidence: 99%

“…The second and third installments of NHANES, between 1976–1980 and 1988–1994 respectively, demonstrated significant folate deficiencies (serum folate < 6.81nM) in some populations. (2, 3) Due to the findings that folic acid supplementation could help reduce fetal neural tube defects,(4) fortification of U.S. cereal-grain products became mandatory in 1998. Population based analysis since that time has shown, on average, an approximately 2.5 fold increase in serum folate concentrations compared to pre-fortification.…”

Section: Introductionmentioning

confidence: 99%

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Divergence between dietary folate intake and concentrations in the serum and red blood cells of aging males in the United States

2016

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Background and Aims As part of a broader study examining the relationship between serum folate concentrations and prostate cancer progression, we determined if there are age related changes in serum folate concentration compared to folate intake in the U.S. male population. Methods Weighted data from the 2007–2008 and 2009–2010 NHANES databases was analyzed. A subpopulation of male participants was selected who were older than one year of age, had completed two days of dietary recall including supplement usage, and had fasted for at least 4 hours prior to having their serum folate measured. Total dietary folate equivalent (DFE) intake (mcg) represented the combination of all natural food folate and folic acid from fortification and dietary supplements. Geometric means of serum folate (nM), red blood cell (RBC) folate (nM), and DFE intake were calculated for nine consecutive age groups, with each group generally representing a 10 year span. Analysis was then focused on males older than 20 years of age. Results A total of 19,142 subjects were in the initial NHANES population, which represented over 294 million people within the United States. Applying our inclusion criteria created a final subpopulation size of 3,775. Subsequent analysis of the age groups for all males older than 20 years found the following: The mean serum folate (nM) with 95% CI levels ranged from 28.2 (26.6, 29.9) to 55.1 (47.5, 63.9). RBC folate (nM) concentrations with 95% CI levels without any fasting exclusions ranged from 795.6 (741.5, 853.7) to 1038.4 (910.7, 1184.2). Serum and RBC folate concentrations were significantly higher with age across these age groups (p<0.001). However, the mean total daily DFE intake did not significantly differ ranging from 640.4 (574.7, 713.7) to 720.2 (665, 780) mcg, (p=0.373). Serum folate concentrations in men with total daily DFE intake of at least 1000 mcg increased more significantly with increasing age than serum folate concentrations in men with less than 400 mcg of total daily DFE intake (p<0.001). There was a similar trend with the RBC folate concentrations (p=0.054). Conclusions We observed higher serum and RBC folate concentrations and a divergence between dietary folate intake and these folate concentrations in older males. This phenomenon was evident at total DFE intakes that were significantly less than the 1000 mcg tolerable upper intake level currently recommended by the Institute of Medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Divergence between dietary folate intake and concentrations in the serum and red blood cells of aging males in the United States

2016

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“…All drugs were obtained from Sigma–Aldrich Co. The drugs were infused intravesically in concentrations that were determined in pilot experiments or were selected based on concentrations shown in previous studies in rats to be effective in altering reflex bladder activity (Kullmann et al, 2008b; Masuda et al, 2006; Matsumoto et al, 2010, 2012) or bladder afferent nerve activity (Yu and de Groat, 2010; Yu et al, 2016) after intravesical administration.…”

Section: Methodsmentioning

confidence: 99%

“…Activation of cholinergic receptors near the lumenal surface of the bladder by intravesical administration of muscarinic (Kullmann et al, 2008b; Matsumoto et al, 2010) or nicotinic cholinergic receptor agonists (Beckel et al, 2006; Beckel and Birder, 2012; Masuda et al, 2006) modulates reflex bladder activity in spinal cord intact and in chronic spinal cord transected rats (Matsumoto et al, 2012). These effects are attributed to changes in bladder afferent firing.…”

Section: Introductionmentioning

confidence: 99%

Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats

Ungerer

Kim

Daugherty

et al. 2016

Experimental Neurology

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The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C6) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50 μM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250 μM) decreased BC, increased MMP, but did not alter PMC-AUC. The effects of OXO-M on BC and PMC-AUC were suppressed by intravesical administration of AMN (50–100 μM), and the effects of nicotine were blocked by hexamethonium (1 mM). Antagonists infused intravesically alone did not alter reflex bladder activity. However, AMN (0.2 mg/kg, subcutaneously) decreased PMC-AUC. 8-OHDPAT (0.5 mg/kg, s.c.), a 5-HT1A receptor agonist, suppressed the OXO-M-induced decrease in BC but not the enhancement of PMC-AUC. These results indicate that activation of cholinergic receptors located near the lumenal surface of the bladder modulates two types of reflex bladder activity (i.e., micturition and pre-micturition contractions). The effects may be mediated by activation of receptors on suburothelial afferent nerves or receptors on urothelial cells which release transmitters that can in turn alter afferent excitability. The selective action of nicotine on BC, while OXO-M affects both BC and PMC-AUC, suggests that micturition reflexes and PMCs are activated by different populations of afferent nerves. The selective suppression of the OXO-M effect on BC by 8-OH-DPAT without altering the effect on PMCs supports this hypothesis. The failure of intravesical administration of either AMN or hexamethonium alone to alter bladder activity indicates that cholinergic receptors located near the lumenal surface do not tonically regulate bladder reflex mechanisms in the SCI cat.

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“…Previous studies suggested that the non‐voiding contraction (NVC) in SCI rats are mediated predominantly by C‐fiber afferents while A δ‐fiber afferents are involved in voiding reflexes in spinal intact rats. In addition, studies reported that the M 3 receptor may play an important role in the NDO after SCI, though there was no significant difference in M 3 receptor protein expression between SCI rats and normal control . For example, activation of muscarinic receptor could enhance NDO through increasing C‐fiber afferents mediated activity in SCI rats and muscarinic receptor antagonists were implicated in the desensitization of C‐fiber afferents, whereas it is hard to reach the detrusor layer and modulate detrusor muscle activity by intravesical administration .…”

Section: Introductionmentioning

confidence: 99%

Injecting RNA interference lentiviruses targeting the muscarinic 3 receptor gene into the bladder wall inhibits neurogenic detrusor overactivity in rats with spinal cord injury

Shang

Jia

Hao

et al. 2018

Neurourology and Urodynamics

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Aims To investigate the effects of injecting RNA interference (RNAi) lentiviruses targeting the muscarinic 3 (M3) receptor gene into the bladder wall on bladder activity in rats with spinal cord injury (SCI). Methods Four M3 RNAi lentiviruses were constructed and used to infect primary cultured bladder smooth muscle cells (BSMCs). Western blotting and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) were performed to determine the optimal RNAi lentivirus with the highest interference efficiency. Female Wistar rats were subjected spinal cord transection at T9‐10 and randomly divided into three groups (n = 8), namely, blank control, negative control, and experimental groups, and injected into the bladder wall with saline, negative control shRNA, and M3 RNAi lentiviruses, respectively, 1 week after spinal cord transection. The normal rats were used as normal control group. Urodynamic parameters and bladder tissues were evaluated in the different groups. Results An M3 RNAi lentivirus with the highest interference efficiency (78.9%) was constructed and identified. Three weeks after injecting M3 RNAi lentiviruses into the bladder wall, Western blotting and qRT‐PCR showed that the M3 receptor was significantly downregulated in the experimental group. Cystometric evaluation suggested that downregulating M3 receptor expression could substantially decrease basal pressure, residual volume, and non‐voiding contraction number, increase intercontraction interval, and significantly improve bladder compliance in rats with SCI. Conclusion Injecting RNAi lentiviruses targeting the M3 receptor gene into the bladder wall could effectively inhibit neurogenic detrusor overactivity (NDO) due to SCI. Thus, this approach may be a potential treatment for NDO in SCI.

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Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

Cited by 25 publications

References 29 publications

Divergence between dietary folate intake and concentrations in the serum and red blood cells of aging males in the United States

Divergence between dietary folate intake and concentrations in the serum and red blood cells of aging males in the United States

Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats

Injecting RNA interference lentiviruses targeting the muscarinic 3 receptor gene into the bladder wall inhibits neurogenic detrusor overactivity in rats with spinal cord injury

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