RGD Reference Report - PACAP-mediated ATP release from rat urothelium and regulation of PACAP/VIP and receptor mRNA in micturition pathways after cyclophosphamide (CYP)-induced cystitis. - Rat Genome Database

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PACAP-mediated ATP release from rat urothelium and regulation of PACAP/VIP and receptor mRNA in micturition pathways after cyclophosphamide (CYP)-induced cystitis.

Authors: Girard, BM  Wolf-Johnston, A  Braas, KM  Birder, LA  May, V  Vizzard, MA 
Citation: Girard BM, etal., J Mol Neurosci. 2008 Nov;36(1-3):310-20. Epub 2008 Jun 19.
RGD ID: 2315964
Pubmed: PMID:18563302   (View Abstract at PubMed)
PMCID: PMC2737258   (View Article at PubMed Central)
DOI: DOI:10.1007/s12031-008-9104-4   (Journal Full-text)

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 PAC1 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. PAC1 messenger RNA expression significantly (p < or = 0.05) increased in U and DSM after 48 h and chronic CYP-induced cystitis after an initial decrease at 4 h. VPAC1 and VPAC2 transcripts increased in U and DSM after acute and intermediate CYP-induced cystitis followed by a decrease in VPAC2 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 microM). 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 PAC1 regulation in micturition pathways with inflammation and PACAP-mediated ATP release from urothelium.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cystitis  ISOAdcyap1 (Rattus norvegicus)2315964; 2315964mRNA:increased expression:urinary bladder urotheliumRGD 
cystitis  ISOAdcyap1r1 (Rattus norvegicus)2315964; 2315964mRNA:increased expression:urothelium and detrusor muscle (rat)RGD 
cystitis  IEP 2315964mRNA:increased expression:urinary bladder urotheliumRGD 
cystitis  IEP 2315964mRNA:increased expression:urothelium and detrusor muscle (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adcyap1  (adenylate cyclase activating polypeptide 1)
Adcyap1r1  (ADCYAP receptor type I)

Genes (Mus musculus)
Adcyap1  (adenylate cyclase activating polypeptide 1)
Adcyap1r1  (adenylate cyclase activating polypeptide 1 receptor 1)

Genes (Homo sapiens)
ADCYAP1  (adenylate cyclase activating polypeptide 1)
ADCYAP1R1  (ADCYAP receptor type I)


Additional Information