4.4 Article Proceedings Paper

PACAP-Mediated ATP Release from Rat Urothelium and Regulation of PACAP/VIP and Receptor mRNA in Micturition Pathways after Cyclophosphamide (CYP)-Induced Cystitis

期刊

JOURNAL OF MOLECULAR NEUROSCIENCE
卷 36, 期 1-3, 页码 310-320

出版社

HUMANA PRESS INC
DOI: 10.1007/s12031-008-9104-4

关键词

Inflammation; Urinary bladder; Neuropeptides; ATP; Urothelium

资金

  1. NIDDK NIH HHS [R01 DK051369-10, R01 DK060481-04, R01 DK065989-04, DK060481, R01 DK051369-11A1, R01 DK065989, DK051369, R29 DK051369, R56 DK060481, R01 DK060481, R01 DK060481-05A1, R01 DK065989-05, R01 DK051369, DK065989] Funding Source: Medline

向作者/读者索取更多资源

Pituitary adenylate cyclase-activating peptide (PACAP) peptides are expressed in micturition pathways, and PACAP expression is regulated by urinary bladder inflammation. Previous physiological studies have demonstrated roles for PACAP27 and PACAP38 in detrusor smooth muscle (DSM) contraction and a PAC(1) receptor antagonist reduced cyclophosphamide (CYP)-induced bladder hyperreflexia. To gain insight into PACAP signaling in micturition and regulation with cystitis, receptor characterization by real-time quantitative polymerase chain reaction and physiological assays were performed. PACAP receptors were identified in tissues of rat micturition pathway, including DSM, urothelium (U), and dorsal root ganglia (DRG) after acute (4 h), intermediate (48 h) or chronic (8 days) CYP-induced cystitis. PAC(1) messenger RNA expression significantly (p-0.05) increased in U and DSM after 48 h and chronic CYP-induced cystitis after an initial decrease at 4 h. VPAC(1) and VPAC(2) transcripts increased in U and DSM after acute and intermediate CYP-induced cystitis followed by a decrease in VPAC(2) expression with chronic cystitis. Application of PACAP27 (100 nM) to cultured urothelial cells evoked adenosine triphosphate (ATP) release that was blocked by the PAC1 specific antagonist, M65 (1 mu M). PACAP38 (100 nM) also evoked ATP release from cultured urothelial cells, but ATP release was less than that observed with PACAP27. PACAP transcripts were increased in the U with intermediate and chronic cystitis, whereas vasoactive intestinal polypeptide (VIP) expression in both tissues was very low and showed no regulation with cystitis. Regulation of PACAP, galanin, and substance P transcripts expression was observed in lumbosacral DRG, but no regulation for VIP was observed. The current data demonstrate PACAP and PAC(1) regulation in micturition pathways with inflammation and PACAP-mediated ATP release from urothelium.

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