title: Modulation of TRPV1-dependent contractility of normal and diabetic bladder smooth muscle by analgesic toxins from sea anemone Heteractis crispa.
abstract: OBJECTIVE
  TRPV1-expressing, capsaicin (CAP)-sensitive afferent fibers innervating bladder in addition to sensory function also exhibit "efferent" features consisting in TRPV1-dependent release of tachykinins (TAC) affecting detrusor smooth muscle (DSM) contractions. Our aim was to investigate the effects of two novel polypeptide inhibitors of TRPV1 from the venom of tropical sea anemone Heteractis crispa, APHC1 and APHC3, on the contractions of DSM from bladders of normal and diabetic rats.
  
  
  METHODS
  Experiments were conducted on urothelium-devoid DSM strips from normal rats and rats 8weeks after streptozotocin-induced diabetes by means of contraction force measurements.
  
  
  RESULTS
  Pre-exposure of DSM strips to APHC1 or APHC3 (200nM) specifically inhibited CAP-induced, TRPV1-dependent contractions. Both peptides also transiently enhanced basal tone and spontaneous contractions of DSM strips followed by delayed suppression of electric field stimulation (EFS)-evoked nonadrenergic-noncholinergic (NANC) contractions. The decrease of the amplitude of EFS-evoked NANC contractions by АРНС1 or АРНС3 reached 38.5±3.4% and 25.1±1.6%, respectively, in normal DSM strips and 46.3±3.3% and 43.9±1.8%, respectively, in diabetic ones. APHC-peptide-induced transient enhancement of basal tone could be mimicked by serine protease inhibitor, 4-(2-aminoethyl)bezenesulfonyl fluoride (300 μM).
  
  
  CONCLUSIONS
  Our results demonstrate that АРНС1 and АРНС3 may be considered as effective inhibitors of bladder contractility especially during diabetic cystopathy. Modality of action of APHC-polypeptides via the mechanisms involving decreased TRPV1-dependent release of TAC from bladder afferents and suppression of TAC degradation due to their activity as endogenous proteases inhibitors is proposed.
authors.affiliation: Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Philyppov
authors.forename: Oksana N
authors.initials: ON
authors.lastname: Paduraru
authors.forename: Yaroslav A
authors.initials: YA
authors.lastname: Andreev
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Grishin
authors.forename: Yaroslav M
authors.initials: YM
authors.lastname: Shuba
mesh_terms: D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003064:Cnidarian Venoms / Q000302:isolation & purification / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004558:Electric Stimulation; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008387:Marine Toxins / Q000302:isolation & purification / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012615:Sea Anemones; D050916:TRPV Cation Channels / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D003064:Cnidarian Venoms; D036341:Intercellular Signaling Peptides and Proteins; D008387:Marine Toxins; D010455:Peptides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C577093:analgesic polypeptide HC1, Heteractis crispa; C577094:analgesic polypeptide HC3, Heteractis crispa; D002211:Capsaicin