Expression of phosphorylated cAMP response element binding protein (p-CREB) in bladder afferent pathways in VIP-/- mice with cyclophosphamide (CYP)-induced cystitis.
The expression of phosphorylated cAMP response element binding protein (p-CREB) in dorsal root ganglia (DRG) with and without cyclophosphamide (CYP)-induced cystitis (150 mg/kg, i.p; 48 h) was determined in VIP(-/-) and wild-type (WT) mice. p-CREB immunoreactivity (IR) was determined in bladder (Fast blue) afferent cells. Nerve growth factor (NGF) bladder content was determined by enzyme-linked immunosorbent assays. Basal expression of p-CREB-IR in DRG of VIP(-/-) mice was (p < or = 0.01) greater in L1, L2, L5-S1 DRG compared to WT mice. CYP treatment in WT mice increased (p < or = 0.05) p-CREB-IR in L1, L2, L5-S1 DRG. CYP treatment in VIP(-/-) mice (p < or = 0.01) increased (p < or = 0.01) p-CREB-IR in L6-S1 DRG compared to WT with CYP. In WT mice, bladder afferent cells (20-38%) in DRG expressed p-CREB-IR under basal conditions. With CYP, p-CREB-IR increased in bladder afferent cells (60-65%; L6-S1 DRG) in WT mice. In VIP(-/-) mice, bladder afferent cells (12-58%) expressed p-CREB-IR under basal conditions, and CYP increased p-CREB expression (78-84%) in L6-S1 DRG. Urinary bladder NGF expression in VIP(-/-) mice under basal conditions or after cystitis was significantly greater than WT. Detrusor smooth muscle thickness was significantly increased in VIP(-/-) mice. Bladder NGF expression may contribute to differences in p-CREB expression.
Jensen
Dorthe G
DG
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
Studeny
Simon
S
May
Victor
V
Waschek
James
J
Vizzard
Margaret A
MA
D000344:Afferent Pathways / Q000378:metabolism*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003520:Cyclophosphamide / Q000494:pharmacology*; D003556:Cystitis / Q000139:chemically induced*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D010766:Phosphorylation; D001743:Urinary Bladder / Q000294:innervation* / Q000473:pathology / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D014660:Vasoactive Intestinal Peptide; D003520:Cyclophosphamide; D020932:Nerve Growth Factor