Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats

Matsuta, Yosuke; Yusup, Anwar; Tanase, Kazuya; Ishida, Hirokazu; Akino, Hironobu; Yokoyama, Osamu

doi:10.1016/j.juro.2010.03.002

Cited by 34 publications

(26 citation statements)

References 28 publications

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“…However, there are also reports in rats showing that bicuculline (iv or icv) can produce variable responses including a transient inhibition of isovolumetric bladder contractions, a significant increase in bladder capacity, or no effect (14,17,21). These variable responses might be due to variations in dosages or routes of administration in different studies.…”

Section: Discussionmentioning

confidence: 99%

Role of spinal GABA_Areceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

Xiao

Reese

Schwen

et al. 2014

American Journal of Physiology-Renal Physiology

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Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly (P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly (P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly (P < 0.05) reduced 2T PNS inhibition at low doses (0.01-0.1 mg/kg). During saline cystometry, PNS significantly (P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03-0.3 mg/kg iv) also significantly (P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.

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Section: Discussionmentioning

confidence: 99%

Role of spinal GABA_Areceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

Xiao

Reese

Schwen

et al. 2014

American Journal of Physiology-Renal Physiology

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“…These effects are reversed by bicuculline, a GABA A receptor antagonist; and bicuculline alone stimulates bladder activity and lowers the volume threshold for micturition, indicating that the micturition reflex pathway in the PMC and PAG is tonically inhibited by a GABAergic mechanism. Intracerebroventricular administration of melatonin increases bladder capacity in rats; and this effect is blocked by bicuculline indicating that melatonin activates a GABAergic inhibitory mechanism in the brain (414). Intracerebroventricular injection of baclofen, a GABA B agonist, suppresses distention-evoked micturition in urethane-anesthetized rats but unexpectedly this effect is not blocked by phaclofen, a GABA B receptor antagonist (165, 174).…”

Section: Neurotransmitters In Central Pathways Controlling Micturitionmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

Groat

Griffiths

Yoshimura

2014

Comprehensive Physiology

348

527

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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“…Nocturnal production of melatonin is impaired in older adults, and several clinical trials have demonstrated that exogenous administration of melatonin to this group improves sleep [5,6] and habitual nocturnal voiding [7,8]. Melatonin increases bladder capacity and decreases urine volume via a central nervous system (CNS) effect [9] and also relaxes involuntary or increased bladder contractions via peripheral nervous system effects [10]. It is a prime physiological determinant of circadian rhythms and influences the physiological decrease in urine output and frequency at night in healthy individuals, either directly or indirectly through effects on other hormones [1].…”

Section: Introductionmentioning

confidence: 99%

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

Han

Chang

Myung

et al. 2012

Korean J Physiol Pharmacol

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The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10-8~10-6 M) decreased the contractile responses induced by PE (10-9~10-4 M) and Ach (10-9~10-4 M) in a dose-dependent manner. Melatonin (10-7 M) also blocked contraction induced by high KCl ([KCl]ECF; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10-7 M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10-11~10-7 M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.

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Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats

Abstract: Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

Cited by 34 publications

References 28 publications

Role of spinal GABA_Areceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

Role of spinal GABA_Areceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

Neural Control of the Lower Urinary Tract

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

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Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats

Abstract: Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.

Cited by 34 publications

References 28 publications

Role of spinal GABAAreceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

Role of spinal GABAAreceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

Neural Control of the Lower Urinary Tract

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

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Product

Resources

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Role of spinal GABA_Areceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats

Role of spinal GABA_Areceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats