Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies examined changes in the expression of calcitonin gene-related peptide (CGRP) and substance P (SP) in lumbosacral (L6-S1) micturition reflex pathways, following chronic cystitis induced by cyclophosphamide (CYP). In control Wistar rats, CGRP- or SP-immunoreactivity (IR) was expressed in fibers in the superficial dorsal horn in all segmental levels examined (L4-S1). Bladder afferent cells in the dorsal root ganglia (DRG; L6, S1) from control animals also exhibited CGRP- (41-55%) or SP-IR (2-3%). Following chronic, CYP-induced cystitis, CGRP- and SP-IR were dramatically increased in spinal segments and DRG (L6, S1) involved in micturition reflexes. The density of CGRP- and SP-IR was increased in the superficial laminae (I-II) of the L6 and S1 spinal segments. No changes in CGRP- or SP-IR were observed in the L4-L5 segments. Staining was also dramatically increased in a fiber bundle extending ventrally from Lissauer's tract in lamina I along the lateral edge of the DH to the sacral parasympathetic nucleus in the L6-S1 spinal segments. Following chronic cystitis, CGRP- and SP-IR in cells in the L6 and S1 DRG significantly (P< or =0.05) increased and the percentage of bladder afferent cells expressing CGRP- (76%) or SP-IR (11-18%) also significantly (P< or =0.001) increased. No changes were observed in the L4-L5 DRG. These studies suggest that the neuropeptides, CGRP and SP, may play a role in urinary bladder afferent pathways, following chronic urinary bladder inflammation. Changes in CGRP or SP expression following cystitis may contribute to the altered visceral sensation (allodynia) and/or urinary bladder hyperreflexia in the clinical syndrome, interstitial cystitis.
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PMID:Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis. 1131 54

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.
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PMID:PACAP-mediated ATP release from rat urothelium and regulation of PACAP/VIP and receptor mRNA in micturition pathways after cyclophosphamide (CYP)-induced cystitis. 1856 2