Neuroplasticity of PACAP Expression and Function in Micturition Reflex Pathways

Gonzalez, Eric J.; Girard, Beatrice M.; Braas, Karen M.; May, Víctor; Vizzard, Margaret A.

doi:10.1007/978-3-319-35135-3_19

Cited by 3 publications

(8 citation statements)

References 127 publications

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“…We previously demonstrated an upregulation of PACAP expression in rodent micturition pathways following CYP-induced cystitis ( Braas et al, 2006 ). We have subsequently examined the effects of CYP-induced cystitis (4 h, 48 h, chronic) in PACAP promoter-dependent EGFP BAC transgenic mice (gift from Dr. James A. Waschek, David Geffen School of Medicine, University of California, Los Angeles) ( May et al, 2015 , 2017a ; Gonzalez et al, 2016 ). In control mice with no CYP treatment, low basal expression of PACAP-EGFP+ fibers and cells was present in the superficial DH (L1, L2, L4-S1) and DRG (L1, L2, L6, S1) examined.…”

Section: Pacap Expression In Lut With Cyp-induced Cystitis In Pacap Pmentioning

confidence: 99%

“…PACAP/PAC1 receptor transcripts are increased in specific limbic structures following RVS exposure; CNS PACAP signaling is anxiogenic and anorexic, and chronic stress-induced anxiety-related behaviors can be blocked by PAC1 receptor antagonists ( Hammack et al, 2009 ; Lezak et al, 2014a , b ; Missig et al, 2014 ; Roman et al, 2014 ). We have recently characterized PACAP/PAC1 signaling in stress-induced urinary bladder dysfunction in mice ( Gonzalez et al, 2016 ; May et al, 2017b ). RVS induced urinary bladder hyperreflexia characterized by reduced void volumes, increased voiding frequency and decreased intercontraction void intervals ( Merrill et al, 2013b ; Merrill and Vizzard, 2014 ).…”

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

“…No changes were observed in PAC1 mRNA expression in lumbosacral DRG examined; however, PAC1 protein was significantly increased in L6 an S1 DRG. Bladder function was assessed in RVS and control mouse groups using continuous, intravesical infusion of saline in conscious, unrestrained mice with an open outlet both before and after PAC1 blockade at the level of the urinary bladder ( Gonzalez et al, 2016 ; May et al, 2017b ). Intravesical administration of the PAC1 receptor antagonist, PACAP(6-38) (300 nM), significantly increased intercontraction interval (2.5-fold) and void volume (2.5-fold) in mice following RVS ( Gonzalez et al, 2016 ; May et al, 2017b ).…”

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

“…Bladder function was assessed in RVS and control mouse groups using continuous, intravesical infusion of saline in conscious, unrestrained mice with an open outlet both before and after PAC1 blockade at the level of the urinary bladder ( Gonzalez et al, 2016 ; May et al, 2017b ). Intravesical administration of the PAC1 receptor antagonist, PACAP(6-38) (300 nM), significantly increased intercontraction interval (2.5-fold) and void volume (2.5-fold) in mice following RVS ( Gonzalez et al, 2016 ; May et al, 2017b ). We also evaluated the effect of PAC1 blockade at the level of the urinary bladder on pelvic and hindpaw sensitivity in RVS or control mouse groups using von Frey filament testing.…”

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

“…We also evaluated the effect of PAC1 blockade at the level of the urinary bladder on pelvic and hindpaw sensitivity in RVS or control mouse groups using von Frey filament testing. Intravesical administration of PACAP(6-38) (300 nM) significantly reduced pelvic and hindpaw sensitivity in mice following RVS ( Gonzalez et al, 2016 ; May et al, 2017b ). PACAP/receptor signaling contributes to the increased voiding frequency and pelvic and hindpaw sensitivity observed in mice following RVS ( Figure 5 ) ( Braas et al, 2006 ).…”

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

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PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

Girard

Tooke

Vizzard

2017

Front. Syst. Neurosci.

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Complex organization of CNS and PNS pathways is necessary for the coordinated and reciprocal functions of the urinary bladder, urethra and urethral sphincters. Injury, inflammation, psychogenic stress or diseases that affect these nerve pathways and target organs can produce lower urinary tract (LUT) dysfunction. Numerous neuropeptide/receptor systems are expressed in the neural pathways of the LUT and non-neural components of the LUT (e.g., urothelium) also express peptides. One such neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the LUT. Mice with a genetic deletion of PACAP exhibit bladder dysfunction and altered somatic sensation. PACAP and associated receptors are expressed in the LUT and exhibit neuroplastic changes with neural injury, inflammation, and diseases of the LUT as well as psychogenic stress. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency in preclinical animal models and transgenic mouse models that mirror some clinical symptoms of bladder dysfunction. A change in the balance of the expression and resulting function of the PACAP/receptor system in CNS and PNS bladder reflex pathways may underlie LUT dysfunction including symptoms of urinary urgency, increased voiding frequency, and visceral pain. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction.

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Section: Pacap Expression In Lut With Cyp-induced Cystitis In Pacap Pmentioning

confidence: 99%

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

Section: Rvs and Pacap/receptor Mechanisms Contribute To Micturition mentioning

confidence: 99%

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PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

Girard

Tooke

Vizzard

2017

Front. Syst. Neurosci.

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PACAP38-Mediated Bladder Afferent Nerve Activity Hyperexcitability and Ca2+ Activity in Urothelial Cells from Mice

et al. 2018

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Pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate PAC1 receptor (Adcyap1r1) have tissue-specific distributions in the lower urinary tract (LUT). The afferent limb of the micturition reflex is often compromised following bladder injury, disease, and inflammatory conditions. We have previously demonstrated that PACAP signaling contributes to increased voiding frequency and decreased bladder capacity with cystitis. Thus, the present studies investigated the sensory components (e.g., urothelial cells, bladder afferent nerves) of the urinary bladder that may underlie the pathophysiology of aberrant PACAP activation. We utilized bladder-pelvic nerve preparations and urothelial sheet preparations to characterize PACAP-induced bladder afferent nerve discharge with distention and PACAP-induced Ca activity, respectively. We determined that PACAP38 (100 nM) significantly (p ≤ 0.01) increased bladder afferent nerve activity with distention that was blocked with a PAC1/VPAC2 receptor antagonist PACAP6-38 (300 nM). PACAP38 (100 nM) also increased Ca activity in urothelial cells over that observed in control preparations. Taken together, these results establish a role for PACAP signaling in bladder sensory components (e.g., urothelial cells, bladder afferent nerves) that may ultimately facilitate increased voiding frequency.

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Intrabladder PAC1 Receptor Antagonist, PACAP(6-38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in Mice Exposed to Repeated Variate Stress (RVS)

et al. 2020

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Neuroplasticity of PACAP Expression and Function in Micturition Reflex Pathways

Cited by 3 publications

References 127 publications

PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

PACAP38-Mediated Bladder Afferent Nerve Activity Hyperexcitability and Ca2+ Activity in Urothelial Cells from Mice

Intrabladder PAC1 Receptor Antagonist, PACAP(6-38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in Mice Exposed to Repeated Variate Stress (RVS)

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