Modulation of TRPV1-dependent contractility of normal and diabetic bladder smooth muscle by analgesic toxins from sea anemone Heteractis crispa
| Autor: | Eugene V. Grishin, Yaroslav A. Andreev, Igor B. Philyppov, Oksana N. Paduraru, Yaroslav M. Shuba |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Proteases Contraction (grammar) Urinary Bladder TRPV1 TRPV Cation Channels Biology General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental Contractility chemistry.chemical_compound Cnidarian Venoms Internal medicine medicine Animals Rats Wistar General Pharmacology Toxicology and Pharmaceutics Analgesics Urinary bladder Muscle Smooth General Medicine Electric Stimulation Rats Sea Anemones medicine.anatomical_structure Endocrinology chemistry Capsaicin Intercellular Signaling Peptides and Proteins Marine Toxins medicine.symptom Peptides Marine toxin Muscle Contraction Muscle contraction |
| Zdroj: | Life Sciences. 91:912-920 |
| ISSN: | 0024-3205 |
| Popis: | Aims 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. Main methods Experiments were conducted on urothelium-devoid DSM strips from normal rats and rats 8 weeks after streptozotocin-induced diabetes by means of contraction force measurements. Key findings Pre-exposure of DSM strips to APHC1 or APHC3 (200 nM) 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). Significance 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect