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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2009; 55(6): 30-40

Modulation of the contractions of the smooth muscles of the rat vas deferens by trpm8channel activator menthol

I.B. Phylippov , I.A. Vladimirova, E.M. Kulieva, R. Skryma, N. Prevarskaya, YA.M. Shuba

    Ін-т фізіології ім. О.О. Богомольця НАН України, Київ;Міжнарод. центр молекуляр. фізіології НАН України, Київ;Лільськ. ун-т наук та технологій, Франція


TRPM8 is nonselective, Ca2+ permeable cationic channel, which is activated by innocuous cold and by chemical drugs imitators of cooling, menthol, icilin and eucalyptol. TRPM8 expression was detected in the smooth muscle cells of the rat vas defer­ence with preferential localization of the TRPM8 protein to the membrane of sarcoplasmic reticulum (SR). In the present work we have studied the effects of TRPM8 channel agonist, menthol, on the contractions of the smooth muscle strips of the epididimal and prostatic portions of the rat vas deferens evoked by potassium rich (KCl) Krebs solution and by muscarinic or adrenergic agonists carbachol (CCh) or noradrenalin (Nor). Menthol (0.1-1 mmol/l) per se virtually unaffected the basal tone, but inhibited in a dose-dependent manner KCl-, CCh- and Nor-evoked contractions of both parts of the vas deference by 30-50%. Blockade of the Ca2+-ATPase of the SR with cyclopiazonic acid (CPA, 10 umol/l) enhanced inhibitory action of menthol on KCl-induced contractions, but slightly decreased inhibition by menthol of agonist-induced ones. Nonspecific TRPM8 blocker, capsazepine (10 umol/l), did not eliminate, but augmented inhibitory action of menthol on all types of contractions. Our data propose that menthol inhibits contractions via two mechanisms: partial blockade of Ca2+ entry via the voltage-gated, L-type calcium channels and a decrease of the calcium storage capacity of the SR. The latter mechanism at least in part is mediated by the SR-resident TRPM8 channel, which by activation of menthol leads to the enhancement of passive leak of Ca2+ from the SR and reduction in the amount of the releasable calcium during activation of contractions.


  1. Болдырев А.И., Соткис А.В., Кулиева Е.М. и др. Экспрессия холодового рецептора TRPM8 в гладких мышцах семявыносящих протоков крысы // Фізіол. журн. - 2009. - 55, № 5 - С.
  2. Amobi N.I., Smith I.C. Different actions in the rat prostatic and epididymal vas deferens of cyclopiazonic acid or ryanodine on noradrenaline-induced contractions // Gen. Pharmacol. - 1999. - 32, № 2. - P. 271-278.
  3. Bidaux G., Flourakis M., Thebault S. et al. Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function // J. Clin. Invest. - 2007. -117, №6. - P. 1647-1657.
  4. Daniels R.L., Takashima Y., McKemy D.D. Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phospho-inositol 4,5-bisphosphate // J. Biol. Chem. - 2009. -284, №3. - P. 1570-1582.
  5. Docherty R.J., Yeats J.C., Piper A.S. Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture // Brit. J. Pharmacol. - 1997. - 121, № 7. - P. 1461-1467.
  6. Ganitkevich V.Ya., Shuba M.F., Smirnov S.V. Calcium-dependent inactivation of potential-dependent calcium inward current in an isolated guinea-pig smooth muscle cell // J. Physiol. - 1987. - 392. - P. 431-449.
  7. Ito S., Kume H., Shiraki A. et al. Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction // Pulm. Pharmacol. Ther. - 2008. -21, №5. -P. 812-817.
  8. Kraft R., Harteneck C. The mammalian melastatin-related transient receptor potential cation channels: an overview // Pflug. Arch. - 2005. - 451, № 1. - P. 204-211.
  9. 9. Langton P.D., Huddart H. Voltage and time dependency of calcium mediated phasic and tonic responses in rat vas deferens smooth muscle the effect of some calcium agonist and antagonist agents // Gen. Pharmacol. - 1988. -19, № 6. - P. 775-787.
  10. 10. Mahieu F., Owsianik G., Verbert al. TRPM8-in-dependent menthol-induced Ca2+ release from endo-plasmic reticulum and Golgi // J. Biol. Chem. - 2007. -282, №5. - P. 3325-3336.
  11. McKemy D.D., Neuhausser W.M., Julius D. Identifi­cation of a cold receptor reveals a general role for TRP channels in thermosensation // Nature. - 2002. -416(6876). - P. 52-58.
  12. Palade P. Drug-induced Ca2+ release from isolated sar­coplasmic reticulum. II. Releases involving a Ca2+-in-duced Ca2+ release channel // J. Biol. Chem. - 1987. -262, №13. - P. 6142-6148.
  13. Peier A.M., Moqrich A., Hergarden A.C. et al. A TRP channel that senses cold stimuli and menthol // Cell. - 2002. - 108, №5. - P. 705-715.
  14. Swandulla D., Carbone E., Schafer K., Lux H.D. Effect of menthol on two types of Ca currents in cultured sensory neurons of vertebrates // Pflug. Arch. - 1987. - 409. - P. 52-59.
  15. Thebault S., Lemonnier L., Bidaux G. et al. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activa­tion of store-operated channels in LNCaP human pros­tate cancer epithelial cells // J. Biol. Chem. - 2005. -280, №47. - P. 39423-39435.
  16. Voets T, Owsianik G, Nilius B. TRPM8 // Handb. Exp. Pharmacol. - 2007. - 179. - P. 329-344.

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