title: PACAP/VIP and receptor characterization in micturition pathways in mice with overexpression of NGF in urothelium.
abstract: Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting or proliferation in the urinary bladder, produces urinary bladder hyperreflexia, and results in increased referred somatic hypersensitivity. Additional NGF-mediated changes might contribute to the urinary bladder hyperreflexia and pelvic hypersensitivity observed in these transgenic mice such as upregulation of neuropeptide/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific, uroplakin II promoter. In the present study, we examined pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), and associated receptor (PAC1, VPAC1, VPAC2) transcripts or protein expression in urothelium and detrusor smooth muscle and lumbosacral dorsal root ganglia in NGF-overexpressing and littermate wildtype mice using real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemical approaches. Results demonstrate upregulation of PAC1 receptor transcript and PAC1-immunoreactivity in urothelium of NGF-OE mice whereas PACAP transcript and PACAP-immunoreactivity were decreased in urothelium of NGF-OE mice. In contrast, VPAC1 receptor transcript was decreased in both urothelium and detrusor smooth muscle of NGF-OE mice. VIP transcript expression and immunostaining was not altered in urinary bladder of NGF-OE mice. Changes in PACAP, VIP, and associated receptor transcripts and protein expression in micturition pathways resemble some, but not all, changes observed after induction of urinary bladder inflammation known to involve NGF production.
authors.affiliation: Department of Anatomy and Neurobiology, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Girard
authors.forename: Susan E
authors.initials: SE
authors.lastname: Malley
authors.forename: Karen M
authors.initials: KM
authors.lastname: Braas
authors.forename: Victor
authors.initials: V
authors.lastname: May
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Vizzard
mesh_terms: D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D008161:Lumbosacral Region / Q000294:innervation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014554:Urination / Q000502:physiology*; D019459:Urothelium / Q000166:cytology / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D020932:Nerve Growth Factor
references.citation: Regul Pept. 2002 Nov 15;109(1-3):89-101
references.pmid: 12409220
references.citation: Ann N Y Acad Sci. 2000;921:390-4
references.pmid: 11193862
references.citation: Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):679-83
references.pmid: 7846036
references.citation: Ann N Y Acad Sci. 2006 Jul;1070:330-6
references.pmid: 16888187
references.citation: Int J Urol. 2005 Oct;12(10):875-80
references.pmid: 16323980
references.citation: J Cell Biol. 2005 Dec 5;171(5):835-44
references.pmid: 16330712
references.citation: Auton Neurosci. 2010 Feb 16;153(1-2):33-40
references.pmid: 19666243
references.citation: Exp Neurol. 2005 Mar;192(1):46-59
references.pmid: 15698618
references.citation: Pain. 2009 Jan;141(1-2):143-50
references.pmid: 19091468
references.citation: J Urol. 2001 Sep;166(3):1111-8
references.pmid: 11490308
references.citation: Eur J Neurosci. 2001 Jul;14(2):267-82
references.pmid: 11553278
references.citation: Ann N Y Acad Sci. 1996 Dec 26;805:204-16; discussion 217-8
references.pmid: 8993404
references.citation: Eur Respir J. 1999 Aug;14(2):443-51
references.pmid: 10515428
references.citation: J Physiol. 2004 Jan 15;554(Pt 2):519-28
references.pmid: 14578481
references.citation: J Urol. 2000 Mar;163(3):1009-15
references.pmid: 10688040
references.citation: J Comp Neurol. 2004 Aug 2;475(4):590-603
references.pmid: 15236239
references.citation: Endocrinology. 1991 Nov;129(5):2787-9
references.pmid: 1935809
references.citation: Neurosci Lett. 1990 Jan 22;108(3):314-20
references.pmid: 2304650
references.citation: J Comp Neurol. 2000 May 8;420(3):335-48
references.pmid: 10754506
references.citation: J Neurochem. 2002 Sep;82(5):1199-207
references.pmid: 12358767
references.citation: J Biol Chem. 1999 Sep 24;274(39):27702-10
references.pmid: 10488112
references.citation: Neuroscience. 2003;120(2):325-31
references.pmid: 12890505
references.citation: Neuroscience. 1998 Apr;83(4):1261-72
references.pmid: 9502264
references.citation: Urology. 2008 Jul;72(1):104-8; discussion 108
references.pmid: 18400272
references.citation: Pharmacol Rev. 2000 Jun;52(2):269-324
references.pmid: 10835102
references.citation: Urology. 2007 Sep;70(3):463-8
references.pmid: 17905097
references.citation: Brain Res Bull. 1983 Sep;11(3):321-4
references.pmid: 6640363
references.citation: Neurosci Lett. 2006 Jan 16;392(3):193-7
references.pmid: 16203088
references.citation: Jpn J Physiol. 1998 Oct;48(5):301-31
references.pmid: 9852340
references.citation: Brain Res Mol Brain Res. 1992 Nov;16(1-2):143-9
references.pmid: 1281253
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Jul;295(1):R111-22
references.pmid: 18448607
references.citation: Br J Anaesth. 1999 Sep;83(3):442-8
references.pmid: 10655916
references.citation: J Pharmacol Exp Ther. 1999 Jul;290(1):66-75
references.pmid: 10381761
references.citation: Somatosens Mot Res. 1999;16(4):369-81
references.pmid: 10632033
references.citation: Handb Exp Pharmacol. 2009;(194):91-138
references.pmid: 19655106
references.citation: Am J Respir Cell Mol Biol. 1998 Feb;18(2):149-57
references.pmid: 9476901
references.citation: Endocr Rev. 2000 Dec;21(6):619-70
references.pmid: 11133067
references.citation: J Neurosci. 1998 Dec 1;18(23):9766-79
references.pmid: 9822736
references.citation: J Urol. 2008 Jun;179(6):2270-4
references.pmid: 18423678
references.citation: BMC Physiol. 2007 Aug 28;7:9
references.pmid: 17725832
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Mar;298(3):R534-47
references.pmid: 20032263
references.citation: Neuroreport. 1998 May 11;9(7):1455-8
references.pmid: 9631447
references.citation: J Urol. 2001 Apr;165(4):1283-8
references.pmid: 11257702
references.citation: Am J Physiol Regul Integr Comp Physiol. 2000 Apr;278(4):R1027-39
references.pmid: 10749792
references.citation: Agents Actions. 1993;38 Spec No:C28-30
references.pmid: 8317316
references.citation: Physiol Genomics. 2002;9(1):5-13
references.pmid: 11948286
references.citation: Neurosci Lett. 2008 Feb 6;431(3):241-6
references.pmid: 18162309
references.citation: J Comp Neurol. 1992 May 22;319(4):615-23
references.pmid: 1619047
references.citation: J Urol. 2004 Dec;172(6 Pt 1):2434-9
references.pmid: 15538286
references.citation: Am J Physiol Renal Physiol. 2008 Dec;295(6):F1778-89
references.pmid: 18842820
references.citation: Ann N Y Acad Sci. 1996 Dec 26;805:410-26; discussion 427-8
references.pmid: 8993421
references.citation: J Auton Nerv Syst. 1992 May 15;38(3):201-8
references.pmid: 1613209
references.citation: J Mol Neurosci. 2008 Nov;36(1-3):310-20
references.pmid: 18563302
references.citation: Brain Res. 1997 Nov 14;775(1-2):166-82
references.pmid: 9439840
references.citation: Am J Physiol Renal Physiol. 2008 Sep;295(3):F826-36
references.pmid: 18632792
references.citation: Neuropharmacology. 2004 Mar;46(3):449-55
references.pmid: 14975700
references.citation: Acta Physiol Scand. 1994 Oct;152(2):129-36
references.pmid: 7839857
references.citation: Virchows Arch A Pathol Anat Histopathol. 1990;416(5):447-51
references.pmid: 2107633
references.citation: In Vitro Cell Dev Biol Anim. 2000 Jul-Aug;36(7):476-84
references.pmid: 11039497
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R951-62
references.pmid: 16322346
references.citation: Regul Pept. 2002 Jul 15;107(1-3):115-23
references.pmid: 12137973
references.citation: Vascul Pharmacol. 2006 Oct;45(4):221-6
references.pmid: 16891158
references.citation: Am J Physiol Renal Physiol. 2005 Sep;289(3):F489-95
references.pmid: 16093424
references.citation: Regul Pept. 2005 Nov;131(1-3):66-73
references.pmid: 16084604
references.citation: J Neurosci. 1999 Jun 1;19(11):4644-53
references.pmid: 10341262
references.citation: BJU Int. 2001 May;87(7):697-702
references.pmid: 11350415
references.citation: Exp Neurol. 2000 Jan;161(1):273-84
references.pmid: 10683293
references.citation: Dev Neurosci. 1997;19(3):232-46
references.pmid: 9208207
references.citation: Mol Interv. 2007 Feb;7(1):26-41
references.pmid: 17339604
references.citation: Am J Physiol Renal Physiol. 2010 Mar;298(3):F589-600
references.pmid: 20032115
references.citation: Regul Pept. 1992 Nov 20;42(1-2):39-50
references.pmid: 1362001
references.citation: Regul Pept. 1998 Oct 16;77(1-3):69-76
references.pmid: 9809798
references.citation: J Neurochem. 2006 Oct;99(2):499-513
references.pmid: 17029602
references.citation: Urol Res. 2002 Sep;30(4):248-55
references.pmid: 12202943
references.citation: J Urol. 2001 Dec;166(6):2118-20
references.pmid: 11696718
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R677-85
references.pmid: 17537839
references.citation: Regul Pept. 1992 Feb 18;37(3):287-303
references.pmid: 1313597
references.citation: J Urol. 2006 May;175(5):1773-6; discussion 1776
references.pmid: 16600756
references.citation: Urology. 2001 Jun;57(6 Suppl 1):82-8
references.pmid: 11378054
references.citation: Br J Urol. 1993 Apr;71(4):427-9
references.pmid: 8499987
references.citation: Urol Res. 1992;20(4):259-63
references.pmid: 1380745
references.citation: J Comp Neurol. 1995 Aug 28;359(3):443-56
references.pmid: 7499540
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R574-85
references.pmid: 12388444
references.citation: J Comp Neurol. 2005 Sep 5;489(4):501-17
references.pmid: 16025456
references.citation: J Comp Neurol. 2008 Mar 20;507(3):1379-92
references.pmid: 18189308
references.citation: BJU Int. 2004 Apr;93(6):770-6
references.pmid: 15049988
references.citation: Brain Res. 1997 Nov 14;775(1-2):156-65
references.pmid: 9439839
references.citation: J Chem Neuroanat. 2001 Mar;21(2):125-38
references.pmid: 11312054
references.citation: J Urol. 1999 Feb;161(2):438-41; discussion 441-2
references.pmid: 9915421
references.citation: Auton Neurosci. 2006 Jun 30;126-127:380-9
references.pmid: 16651033
references.citation: Scand J Gastroenterol. 1993 Jul;28(7):625-32
references.pmid: 8362218