Effects of 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on receptor-independent and -dependent contractile responses in rat aorta

Effects of 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on receptor-independent and -dependent contractile responses in rat aorta

Background/aim: This study investigates whether 1-(2-trifluoromethylphenyl)-imidazole (TRIM), originally proposed as a nitric oxide synthase inhibitor and also suggested to be an inhibitor of store-operated calcium entry in mouse anococcygeal muscle, inhibits receptor-independent and -dependent responses in rat thoracic aorta. Materials and methods: Cyclopiazonic acid- and serotonin-induced vascular responses were investigated in aortic segments isolated from male Sprague Dawley rats using isolated tissue experiments. Changes in intracellular calcium levels were also monitored via front surface fluorescence measurements in fura-2-loaded embryonic rat vascular smooth muscle cell line A7r5. Results: TRIM inhibited serotonin-mediated vascular contractions without affecting cyclopiazonic acid-induced responses. In addition, TRIM caused a nonlinear rightward shift in the serotonin concentration-response curve, possibly via serotonin receptor modulation. Conclusion: TRIM may have an impact on investigation of tissue-specific receptor-independent and -dependent vascular responses. It may also be used as a lead compound in the development of selective serotonin receptor modulators.

___

  • 1. Handy RL, Harb HL, Wallace P, Gaffen Z, Whitehead KJ, Moore PK. Inhibition of nitric oxide synthase by 1-(2-trifluoromethylphenyl) imidazole (TRIM) in vitro: antinociceptive and cardiovascular effects. Br J Pharmacol 1996; 119: 423-431.
  • 2. Gibson A, Fernandes F, Wallace P, McFadzean I. Selective inhibition of thapsigargin-induced contraction and capacitative calcium entry in mouse anococcygeus by trifluoromethylphenylimidazole (TRIM). Br J Pharmacol 2001; 134: 233-236.
  • 3. Ulak G, Mutlu O, Tanyeri P, Komsuoglu FI, Akar FY, Erden BF. Involvement of serotonin receptor subtypes in the antidepressantlike effect of TRIM in the rat forced swimming test. Pharmacol Biochem Behav 2010; 95: 308-314.
  • 4. Clementi E, Meldolesi J. Pharmacological and functional properties of voltage-independent Ca2+ channels. Cell Calcium 1996; 19: 269-279.
  • 5. Putney JW Jr. A model for receptor-regulated calcium entry. Cell Calcium 1986; 7: 1-12.
  • 6. Berridge MJ. Capacitative calcium entry. Biochem J 1995; 312: 1-11.
  • 7. Parekh AB, Penner R. Store depletion and calcium influx. Physiol Rev 1997; 77: 901-930.
  • 8. Putney JW Jr, McKay RR. Capacitative calcium entry channels. BioEssays 1999; 21: 38-46.
  • 9. Rapport MM, Green AA, Page IH. Serum vasoconstrictor, serotonin; chemical inactivation. J Biol Chem 1948; 176: 1237- 1241. 10. Ellwood AJ, Curtis MJ. Involvement of 5-HT(1B/1D) and
  • 5-HT2A receptors in 5-HT-induced contraction of endotheliumdenuded rabbit epicardial coronary arteries. Br J Pharmacol 1997; 122: 875-884.
  • 11. Yuan XJ, Bright RT, Aldinger AM, Rubin LJ. Nitric oxide inhibits serotonin-induced calcium release in pulmonary artery smooth muscle cells. Am J Physiol 1997; 272: L44-50.
  • 12. Tosun M, Paul RJ, Rapoport RM. Coupling of store-operated Ca++ entry to contraction in rat aorta. J Pharmacol Exp Ther 1998; 285: 759-766.
  • 13. Golovina VA, Blaustein MP. Spatially and functionally distinct Ca2+ stores in sarcoplasmic and endoplasmic reticulum. Science 1997; 275: 1643-1648.
  • 14. Guibert C, Marthan R, Savineau JP. 5-HT induces an arachidonic acid-sensitive calcium influx in rat small intrapulmonary artery. Am J Physiol Lung Cell Mol Physiol 2004; 286: L1228-1236.
  • 15. McFadzean I, Gibson A. The developing relationship between receptor-operated and store-operated calcium channels in smooth muscle. Br J Pharmacol 2002; 135: 1-13.
  • 16. Hardie RC, Minke B. Phosphoinositide-mediated phototransduction in Drosophila photoreceptors: the role of Ca2+ and trp. Cell Calcium 1995; 18: 256-274.
  • 17. Montell C, Rubin GM. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 1989; 2: 1313-1323.
  • 18. Xu SZ, Beech DJ. TrpC1 is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells. Circ Res 2001; 88: 84-87.
  • 19. Beech DJ, Xu SZ, McHugh D, Flemming R. TRPC1 storeoperated cationic channel subunit. Cell Calcium 2003; 33: 433- 440.
  • 20. Tosun M, Erac Y, Selli C, Karakaya N. Sarcoplasmic-endoplasmic reticulum Ca2+ ATPase inhibition prevents endothelin A receptor antagonism in rat aorta. Am J Physiol Heart Circ Physiol 2006; 292: H1961-H1966.
  • 21. Rapoport RM. Effects of norepinephrine on contraction and hydrolysis of phosphatidylinositols in rat aorta. J Pharmacol Exp Ther 1987; 242: 188-194.
  • 22. Selli C, Erac Y, Kosova B, Tosun M. Post-transcriptional silencing of TRPC1 ion channel gene by RNA interference upregulates TRPC6 expression and store-operated Ca2+ entry in A7r5 vascular smooth muscle cells. Vascul Pharmacol 2009; 51: 96- 100.
  • 23. Selli C, Erac Y, Tosun M. Simultaneous measurement of cytosolic and mitochondrial calcium levels: Observations in TRPC1- silenced hepatocellular carcinoma cells. J Pharmacol Toxicol Methods 2015; 72: 29-34.
  • 24. Seidler NW, Jona I, Vegh M, Martonosi A. Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum. J Biol Chem 1989; 264: 17816-17823.
  • 25. Ambudkar IS, Ong HL, Liu X, Bandyopadhyay B, Cheng KT. TRPC1: The link between functionally distinct store-operated calcium channels. Cell Calcium 2007; 44: 213-223.
  • 26. Jung S, Strotmann R, Schultz G, Plant TD. TRPC6 is a candidate channel involved in receptor-stimulated cation currents in A7r5 smooth muscle cells. Am J Physiol Cell Physiol 2002; 282: C347- 359.
  • 27. Brueggemann LI, Markun DR, Henderson KK, Cribbs LL, Byron KL. Pharmacological and electrophysiological characterization of store-operated currents and capacitative Ca2+ entry in vascular smooth muscle cells. J Pharmacol Exp Ther 2006; 317: 488-499.
  • 28. Ghisdal P, Vandenberg G, Morel N. Rho-dependent kinase is involved in agonist-activated calcium entry in rat arteries. J Physiol-London 2003; 551: 855-867.
  • 29. Maruyama T, Kanaji T, Nakade S, Kanno T, Mikoshiba K. 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem 1997; 122: 498-505. 30. Iwasaki H, Mori Y, Hara Y, Uchida K, Zhou H, Mikoshiba K.
  • 2-Aminoethoxydiphenyl borate (2-APB) inhibits capacitative calcium entry independently of the function of inositol 1,4,5-trisphosphate receptors. Receptors Channels 2001; 7: 429- 439.
  • 31. Bootman MD, Collins TJ, Mackenzie L, Roderick HL, Berridge MJ, Peppiatt CM. 2-Aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release. FASEB J 2002; 16: 1145- 1150.
  • 32. Ma HT, Patterson RL, van Rossum DB, Birnbaumer L, Mikoshiba K, Gill DL. Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels. Science 2000; 287: 1647-1651.
  • 33. Mehta D, Ahmmed GU, Paria BC, Holinstat M, VoynoYasenetskaya T, Tiruppathi C, Minshall RD, Malik AB. RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability. J Biol Chem 2003; 278: 33492-33500.
  • 34. Handy RL, Wallace P, Gaffen ZA, Whitehead KJ, Moore PK. The antinociceptive effect of 1-(2-trifluoromethylphenyl) imidazole (TRIM), a potent inhibitor of neuronal nitric oxide synthase in vitro, in the mouse. Br J Pharmacol 1995; 116: 2349-2350.
  • 35. Gruetter CA, Lemke SM, Anestis DK, Szarek JL, Valentovic MA. Potentiation of 5-hydroxytryptamine-induced contraction in rat aorta by chlorpheniramine, citalopram and fluoxetine. Eur J Pharmacol 1992; 217: 109-118.
  • 36. Grandaw PP, Purdy RE. Serotonin-induced vasoconstriction in rabbit femoral artery: Mediation by both 5-HT2 serotonergic and alpha(1)-adrenoceptors. J Cardiovasc Pharmacol 1996; 27: 854-860.
  • 37. Florian JA, Watts SW. Integration of mitogen-activated protein kinase kinase activation in vascular 5-hydroxytryptamine2A receptor signal transduction. J Pharmacol Exp Ther 1998; 284: 346-355.