P2X2 and P2X3 receptor expression in human bladder urothelium and changes in interstitial cystitis

被引:108
作者
Tempest, HV
Dixon, AK
Turner, WH
Elneil, S
Sellers, LA
Ferguson, DR
机构
[1] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England
[2] Addenbrookes Hosp, Dept Urol, Cambridge CB2 2QQ, England
[3] Babraham Inst, Cambridge, England
关键词
human; bladder; urothelium; P2X(2); P2X(3); interstitial cystitis;
D O I
10.1111/j.1464-410X.2004.04858.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE To investigate whether the expression of P2X(3) receptors (implicated in the pathophysiology of pain) is altered in human bladder urothelium from patients with interstitial cystitis (IC, a major symptom of which is pain), and as P2X(2) receptors can be co-expressed with P2X(3) receptors, to assess their expression also. PATIENTS AND METHODS Bladder tissue samples were collected from patients undergoing cystectomy or radical prostatectomy. Patients with IC were diagnosed using the international criteria. RNA protein expression levels of both receptors were evaluated using reverse transcription-polymerase chain reaction (PCR), real-time quantitative PCR and Western blot analysis. RESULTS P2X(2) was expressed in the human urothelium, in a glycosylated form. There was less gene expression of P2X(3) in IC urothelium, whereas P2X(2) gene expression was unchanged. This contrasted with the protein expression, which was increased for both P2X(2) and P2X(3). CONCLUSION This is the first report of the expression of the P2X(2) receptor in human bladder urothelium. There was greater protein expression of both P2X(2) and P2X(3) in IC bladder urothelium which did not directly correlate with the gene expression. Changes in expression of P2X(2) and P2X(3) receptors may contribute to the pain that patients with IC have, and might provide novel drug targets.
引用
收藏
页码:1344 / 1348
页数:5
相关论文
共 26 条
[11]   SUMMARY OF THE NATIONAL-INSTITUTE-OF-ARTHRITIS-DIABETES-DIGESTIVE-AND-KIDNEY-DISEASESWORKSHOP ON INTERSTITIAL CYSTITIS, NATIONAL-INSTITUTES-OF-HEALTH, BETHESDA, MARYLAND, AUGUST 28-29, 1987 [J].
GILLENWATER, JY ;
WEIN, AJ .
JOURNAL OF UROLOGY, 1988, 140 (01) :203-206
[12]   Integrated genomic and proteomic analyses of a systematically perturbed metabolic network [J].
Ideker, T ;
Thorsson, V ;
Ranish, JA ;
Christmas, R ;
Buhler, J ;
Eng, JK ;
Bumgarner, R ;
Goodlett, DR ;
Aebersold, R ;
Hood, L .
SCIENCE, 2001, 292 (5518) :929-934
[13]   Evidence for P2X3 receptors in the developing rat brain [J].
Kidd, EJ ;
Miller, KJ ;
Sansum, AJ ;
Humphrey, PPA .
NEUROSCIENCE, 1998, 87 (03) :533-539
[14]   Proteomics and the kidney [J].
Knepper, MA .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2002, 13 (05) :1398-1408
[15]   COEXPRESSION OF P2X(2) AND P2X(3) RECEPTOR SUBUNITS CAN ACCOUNT FOR ATP-GATED CURRENTS IN SENSORY NEURONS [J].
LEWIS, C ;
NEIDHART, S ;
HOLY, C ;
NORTH, RA ;
BUELL, G ;
SURPRENANT, A .
NATURE, 1995, 377 (6548) :432-435
[16]   Molecular physiology of P2X receptors [J].
North, RA .
PHYSIOLOGICAL REVIEWS, 2002, 82 (04) :1013-1067
[17]   P2X receptors and their role in female idiopathic detrusor instability [J].
O'Reilly, BA ;
Kosaka, AH ;
Knight, GF ;
Chang, TK ;
Ford, APDW ;
Rymer, JM ;
Popert, R ;
Burnstock, G ;
McMahon, SB .
JOURNAL OF UROLOGY, 2002, 167 (01) :157-164
[18]   The interstitial cystitis symptom index and problem index [J].
OLeary, MP ;
Sant, GR ;
Fowler, FJ ;
Whitmore, KE ;
SpolarichKroll, J .
UROLOGY, 1997, 49 (5A) :58-63
[19]   Increased prevalence of interstitial cystitis: Previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity [J].
Parsons, CL ;
Dell, J ;
Stanford, EJ ;
Bullen, M ;
Kahn, BS ;
Waxell, T ;
Koziol, JA .
UROLOGY, 2002, 60 (04) :573-578
[20]   Interstitial cystitis: Epidemiology and clinical presentation [J].
Parsons, CL .
CLINICAL OBSTETRICS AND GYNECOLOGY, 2002, 45 (01) :242-249