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Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis.
J Urol. 2000 Dec; 164(6):2119-25.JU

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11061939

Citation

Chiang, G, et al. "Pentosanpolysulfate Inhibits Mast Cell Histamine Secretion and Intracellular Calcium Ion Levels: an Alternative Explanation of Its Beneficial Effect in Interstitial Cystitis." The Journal of Urology, vol. 164, no. 6, 2000, pp. 2119-25.
Chiang G, Patra P, Letourneau R, et al. Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis. J Urol. 2000;164(6):2119-25.
Chiang, G., Patra, P., Letourneau, R., Jeudy, S., Boucher, W., Green, M., Sant, G. R., & Theoharides, T. C. (2000). Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis. The Journal of Urology, 164(6), 2119-25.
Chiang G, et al. Pentosanpolysulfate Inhibits Mast Cell Histamine Secretion and Intracellular Calcium Ion Levels: an Alternative Explanation of Its Beneficial Effect in Interstitial Cystitis. J Urol. 2000;164(6):2119-25. PubMed PMID: 11061939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis. AU - Chiang,G, AU - Patra,P, AU - Letourneau,R, AU - Jeudy,S, AU - Boucher,W, AU - Green,M, AU - Sant,G R, AU - Theoharides,T C, PY - 2000/11/4/pubmed PY - 2001/2/28/medline PY - 2000/11/4/entrez SP - 2119 EP - 25 JF - The Journal of urology JO - J Urol VL - 164 IS - 6 N2 - 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. SN - 0022-5347 UR - https://www.unboundmedicine.com/medline/citation/11061939/Pentosanpolysulfate_inhibits_mast_cell_histamine_secretion_and_intracellular_calcium_ion_levels:_an_alternative_explanation_of_its_beneficial_effect_in_interstitial_cystitis_ DB - PRIME DP - Unbound Medicine ER -