PMID- 11061939
OWN - NLM
STAT- MEDLINE
DCOM- 20010111
LR  - 20181130
IS  - 0022-5347 (Print)
IS  - 0022-5347 (Linking)
VI  - 164
IP  - 6
DP  - 2000 Dec
TI  - Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular 
      calcium ion levels: an alternative explanation of its beneficial effect in 
      interstitial cystitis.
PG  - 2119-25
AB  - PURPOSE: Mast cells are ubiquitous cells derived from the bone marrow and are 
      responsible for allergic reactions as they release numerous vasodilatory, 
      nociceptive and pro-inflammatory molecules in response to immunoglobulin E (IgE) 
      and specific antigen. Mast cell secretion is also triggered by a number of 
      peptides, such as bradykinin and substance P, and may also be involved in the 
      development of inflammatory responses. An example is interstitial cystitis, which 
      is a sterile painful bladder disorder that has been associated with a defective 
      glycosaminoglycan bladder mucosal layer and an increased number of activated mast 
      cells. Pentosanpolysulfate is a synthetic, sulfated polysaccharide that has been 
      approved for the treatment of interstitial cystitis on the premise that it may 
      replenish the defective glycosaminoglycan layer. We hypothesize that 
      pentosanpolysulfate may also have an additional or alternate action on bladder 
      mast cells. We report that pentosanpolysulfate has a powerful dose dependent 
      inhibitory effect on mast cell release of histamine induced by the mast cell 
      secretagogue compound 48/80. MATERIALS AND METHODS: Inhibition of mast cell 
      secretion was documented by light and electron microscopy and extended to 
      stimulation by substance P or IgE and antigen. RESULTS: The inhibition was more 
      potent than that seen with the clinically available mast cell stabilizer disodium 
      cromoglycate (cromolyn). Maximal inhibition by pentosanpolysulfate was apparent 
      within 1 minute, was unaffected by the length of pre-incubation and persisted 
      after the drug was washed off. In contrast, the effect of cromolyn was limited by 
      rapid tachyphylaxis. In addition, while cromolyn has no effect on mucosal or rat 
      basophilic leukemia cells, pentosanpolysulfate inhibited histamine secretion from 
      both. Confocal microscopy using a calcium indicator dye showed that 
      pentosanpolysulfate decreased intracellular calcium ion levels. CONCLUSIONS: 
      Pentosanpolysulfate appears to be a potent inhibitor of allergic and nonimmune 
      mast cell stimulation, which is an alternative explanation of its benefit in 
      interstitial cystitis.
FAU - Chiang, G
AU  - Chiang G
AD  - Department of Pharmacology and Experimental Therapeutics, Tufts University School 
      of Medicine, Boston, Massachusetts, USA.
FAU - Patra, P
AU  - Patra P
FAU - Letourneau, R
AU  - Letourneau R
FAU - Jeudy, S
AU  - Jeudy S
FAU - Boucher, W
AU  - Boucher W
FAU - Green, M
AU  - Green M
FAU - Sant, G R
AU  - Sant GR
FAU - Theoharides, T C
AU  - Theoharides TC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Urol
JT  - The Journal of urology
JID - 0376374
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 33507-63-0 (Substance P)
RN  - 37300-21-3 (Pentosan Sulfuric Polyester)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 4091-50-3 (p-Methoxy-N-methylphenethylamine)
RN  - 9007-28-7 (Chondroitin Sulfates)
RN  - Q2WXR1I0PK (Cromolyn Sodium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Calcium/*metabolism
MH  - Chondroitin Sulfates/pharmacology
MH  - Cromolyn Sodium/pharmacology
MH  - Cystitis, Interstitial/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Histamine Release/*drug effects
MH  - Histocytochemistry
MH  - Immunoglobulin E/pharmacology
MH  - Male
MH  - Mast Cells/*drug effects/metabolism
MH  - Microscopy, Confocal
MH  - Microscopy, Electron
MH  - Pentosan Sulfuric Polyester/*pharmacology
MH  - Peritoneum/cytology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substance P/pharmacology
MH  - Urinary Bladder/cytology
MH  - p-Methoxy-N-methylphenethylamine/pharmacology
EDAT- 2000/11/04 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/04 11:00
PHST- 2000/11/04 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/04 11:00 [entrez]
AID - S0022-5347(05)66981-9 [pii]
PST - ppublish
SO  - J Urol. 2000 Dec;164(6):2119-25.