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PACAP/PAC1 Expression and Function in Micturition Pathways
Jacqueline Ojala1, Katharine Tooke1, Harrison Hsiang1
1Department of Neurological Sciences, The Robert Larner, M.D. College of Medicine at The University of Vermont, Given Building, D405A, Burlington, VT, 05405, USA.
The pituitary adenylate cyclase-activating polypeptide (PACAP) system impacts bladder function. Blocking this system may treat bladder pain syndrome (BPS) and reduce urinary dysfunction.
Area of Science:
- Neuroscience
- Urology
- Pharmacology
Background:
- Neural circuits in the central and peripheral nervous systems control the micturition reflex.
- Neural injury, inflammation, and diseases can impair micturition reflex function.
- The pituitary adenylate cyclase-activating polypeptide (PACAP) receptor system is present in the lower urinary tract (LUT).
Purpose of the Study:
- To investigate the role of the PACAP/PAC1 receptor system in the lower urinary tract.
- To evaluate the therapeutic potential of blocking the PACAP/PAC1 receptor system in bladder pain syndrome (BPS)/interstitial cystitis (IC).
Main Methods:
- Examined PACAP and PAC1 receptor expression, distribution, and function in preclinical models of BPS/IC.
- Assessed the effects of PACAP/PAC1 receptor system blockade on voiding frequency and somatic sensitivity in animal models.
Main Results:
- PACAP and PAC1 receptors are expressed in the LUT and their expression/function changes in BPS/IC models.
- Blocking the PACAP/PAC1 receptor system reduced voiding frequency and somatic sensitivity in preclinical models.
- A transgenic mouse model mimicking BPS/IC symptoms showed similar responses to PACAP/PAC1 receptor blockade.
Conclusions:
- The PACAP/PAC1 receptor system plays a role in micturition pathways.
- Targeting the PACAP/PAC1 receptor system offers a potential therapeutic strategy for LUT dysfunction associated with bladder inflammation and BPS/IC.
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