THE ROLE OF GASOTRANSMITTERS IN REGULATING OF THE FUNCTIONS OF SMOOTH MUSCLES: THE POSSIBLE EFFECTOR SYSTEMS

Influence of gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H2S) on the electrical and contractile activities of smooth muscle cells (SMCs) of the guinea pig ureter and rat aorta were studied by methods of double sucrose bridge and mechanography. It has been shown that CO causes a dose-dependent decrease of the contractile response of SMCs of the ureter and rat aorta and also reduces the amplitude and duration of the action potential plateau. Against the background of the action of biologically active substances, agonists α1-adrenergetic and H1-histaminergetic receptors (phenylephrine and histamine, respectively), these effects of CO donor (CORM II) were amplified. The inhibitory effect of CO on the parameters of the contractile and electrical activities of smooth muscles is attenuated by blocking potassium channels of plasma membrane with tetraethylammonium (TEA) or inhibition of soluble guanylate cyclase (ODQ [1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-l-one]). Thus, the effects of carbon monoxide on the electrical and contractile activities of SMCs are associated with an increase potassium conductivity of the membrane or the activation of soluble guanylate cyclase.

1. Baskakov M.B., Jusubov M.S. Gazovaja ataka, ili Ostorozhno, gazy [Gas attack, or Caution, gases]. Byulleten' sibirskoy mediciny – Bulletin of Siberian Medicine, 2010, vol. 9, no. 6, pp. 160–164 (in Russian).

2. Baskakov M.B., Medvedev M.A., Kovalev I.V., Kapilevich L.V., Zagulova D.V. Mehanizmy reguljacii funkcij gladkih myshc vtorichnymi posrednikami [Mechanisms of regulation of smooth muscles function by the second messengers]. Tomsk, Harbour Publ., 1996. 154 p. (in Russian).

3. Leffler Ch.W., Parfenova H., Jaggar J.H. Carbon monoxide as an endogenous vascular modulator. Am. J. Physiol. Heart Circ. Physiol., 2011, vol. 301, pp. 1–11.

4. Wu L., Wang R. Carbon monoxide: endogenous production, physiological functions and pharmacological applications. Pharmac. Rev., 2005, vol. 57, pp. 585–630.

5. Kamoun P. Endogenous production of hydrogen sulfide in mammals. Amino Asids., 2004, no. 26, pp. 243–254.

6. Wagner C.A. Hydrogen sulfide: a new gaseous signal molecula and blood pressure regulator. Journal of Nephrology, 2009, vol. 22, no. 2, pp. 173–176.

7. Hosoki R., Matsuki N., Kimura H. The possible role of hy-drogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem. Biophys. Res. Commun., 1997, no. 237, pp. 527–531.

8. 8. Peers Ch., Dallas M.L., Scragg J.L. Ion channels as effectors in carbon monoxide signaling. Comm. Integ. Biol,. 2009, vol. 2, pp. 241–242.

9. Wilkinson W.J., Kemp P.G. Carbon monoxide: an emerging regulator of ion channels. J. Physiol., 2011, vol. 589, no. 13, pp. 3055–3062.

10. Lim J.J., Liu Y.H., Khin E.S., Bian J.S. Vasoconstrictive ef-fect of hydrogen sulfide involves downregulation of cAMP in vascular smooth muscle cells. Am. J. Physiol. Cell. Physiol., 2008, vol. 295, pp. 1261–1270.

11. Shuba M.F., Buryj V.A. Membrannye mehanizmy vozbuzhdenija gladkomyshechnyh kletok [Membrane excita-tion mechanisms of smooth muscle cells]. Fiziol. zhurnal, 1984, vol. 30, no. 5, pp. 545–559 (in Russian).

12. Kovalev I.V., Baskakov M.B, Medvedev M.A. i dr. Miogennye jeffekty ciklicheskogo guanozinmonofosfata v gladkomyshechnyh kletkah. Rol' proteinkinazy S. [Myogenic effects of cyclic guanosine monophosphate in smooth muscle cells. The role of protein kinase C]. Ros. fiziol. zhurnal im. Sechenova – Setchenov's Russian Physiological Journal, 2003, vol. 89, no. 4, pp. 436–446 (in Russian).

13. Jaggar J.H., Parfenova H., Liu J. et al. Heme is a carbon monoxide receptor for large-conductance Ca2+-activated K+ channels. Circ. Res., 2007, vol. 97, pp. 805–812.

14. Tang G., Wu L., Liang W., Wang R. Direct stimulation of KATP channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol. Pharmacol., 2005, vol. 68, pp. 1757–1764.

15. Coceani F., Kelsey L., Seidlitz E. Carbon monoxide-induced relaxation of the ductus arteriosus in the lamb: evidence against the prime role of guanylyl cyclase. Br. J. Pharmacol., 1996, vol. 118, pp. 1689–1696.

16. Gusakova S.V., Baskakov M.B., Kovalev I.V. i dr. Vlijanie serovodoroda na sokratitel'nuju aktivnost' gladkomyshechnyh kletok aorty krysy [Influence of the hydrogen sulfide on the contractile smooth muscle activity of the rat aorta]. Byulleten' sibirskoy mediciny – Bulletin of Siberian Medicine, 2010, vol. 9, no. 6, pp. 12–17 (in Russian).