BibTex RIS Kaynak Göster

The mechanism of serotonin induced biphasic effect on pulmonary vessels in the isolated perfused rat lungs

Yıl 2007, Cilt: 9 Sayı: 1, 27 - 35, 01.03.2007

Öz

The aim of this work is detect to serotonin effect, serotonin lidoflazine interactions and possible mechanisms of these effect at isolated perfused rat pulmonary preparation. Lidoflazine, theophylline, methylene blue (MB) and cyproheptadine used in experiments. Lidoflazine is a calcium channel blocker, inhibits nucleoside transport and increase to endogenous adenosine. Theophylline antagonize to adenosine, methylene blue inhibits to guanylate cyclase. Our results show that serotonin caused a biphasic, dose related increase at pulmonary artery perfusion pressure. Early pressure response named as phase-I (F1) and late pressure response named as phase-II (F2). Lidofazine, causes a dose dependent increase at F1 and inhibition at F2. Cyproheptadine causes a dose related inhibition at both F1 and F2 serotonin responses. Our experiments show that, lidoflazine related potentiation of F1 was significantly antagonized by cyproheptadine. Lidoflazine-cyproheptadine combination significantly inhibits to F1 serotonin responses. Cyproheptadine potentiated to lidoflazine’s inhibitory effect to F2. Theophylline increased to F1 but this effect isn’t significant. Theophylline antagonized to lidoflazine’s potentiation of F1, nonsignificantly inhibited to F2 and potentiated to lidoflazine’s effect to this phase. MB inhibited both F1 and F2 and prevent from lidoflazine’s effect to F1. Due to serotonin responses are biphasic, different serotonin receptors may have at pulmonary vascular bed. Lidoflazine’s stimulant effect of F1 may have related to adenosine increas e. Due to F2 depression, lidoflazine may have nonspecific antagonistic effect to serotonin receptors which related to F2. Due to cyproheptadine’s inhibitory effect to F2 is stronger than F1, F1 may have related a different receptor compared to F2. Theophylline’s inhibition of lidoflazine’s F1 increases, indicate that adenosine have a role at this responses. MB experiments show that vascular endothelia have an important role at serotonin responses

Kaynakça

  • Süzer Ö: Serotonin, serotonin reseptörlerinin baslica etki yerleri ve fonksiyonlari: Süzer Farmakoloji. 3. baski: Istanbul. Klinisyen Tip Kitabevleri. 150-4, 2005.
  • Ridley JM, Dooley PC, Milnes JT, Witchel HJ, Hancox JC: Lidoflazine is a high affinity blocker of the HERG K(+) channel. J Mol Cell Cardiol. 36:701-5, 2004.
  • Hugtenburg JG, Mathy MJ, Boddeke HW, Beckeringh JJ, Van Zwieten PA: Differences between negative inotropic and vasodilator effects of calcium antagonists acting on extra and intracellular calcium movements in rat and guinea-pig cardiac preparations. Naunyn Schmiedebergs Arch Pharmacol. 340:567-75, 1989.
  • Barry WH, Horowitz JD, Smith TW : Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells. Br J Pharmacol. 85:51-9, 1985.
  • Boddeke HW, Wilffert B, Heynis JB, Van de Haar Keuken V, Jonkman FA, Van Zwieten PA: A comparison of the cardiac and vasodilatory effects of some calcium entry blockers in perfused isolated guinea-pig hearts. Arch Int Pharmacodyn Ther. 288:175-85, 1987.
  • Engler RL, Gruber HE: Adenosine: An autocoid, in Fozzard HA, Haber E, Jennings RB, et al (eds): The Heart: An Cardiovascular System, New York, Raven Press. pp: 1745- 1764, 1992.
  • Chang-Chun C, Masuda M, Szabo Z, Szerafin T, Szecsi J, Van Belle H, Flameng W: Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping. J Thorac Cardiovasc Surg. 104:1602-9, 1992.
  • Bakhle YS, Reynard AM, Vane JR: Metabolism of the angiotensins in isolated perfused tissues. Nature. 222:956-9, 1969.
  • Burkhalter A, Julius D, Frick OL: Serotonin. Pharmacolgy (edited by Katzung BG) Appleton & Lang. (USA) sixthedition 262-266, 1995.
  • Cohen RA, Shepherd JT, Vanhoutte PM: Inhibitory role of the endothelium in the response of isolated coronary arteries to platelets. Science. 221:273-4, 1983.
  • Humphrey PP, Feniuk W, Perren MJ, Connor HE, Oxford AW, Coates LH, Butina D: GR43175, a selective agonist for the 5-HT1- like receptor in dog isolated saphenous vein. Br J Pharmacol. 94:1123-32, 1988.
  • Küçükhüseyin C: Purinrjik sinir sistemi. Cerrahpasa Tip Fak. Derg. 22:161-170, 1991.
  • Van Zwieten PA: Conclusions on the position of uradipil. Am. J. Cardiol. 64:38-39D, 1989.
  • Eder V, Gautier M, Boissiere J, Girardin C, Rebocho M, Bonnet P. Gamma irradiation induces acetylcholine-evoked, endothelium- independent relaxation and activates K- channels of isolated pulmonary artery of rats. Int J Radiat Oncol Biol Phys. 60:1530-7, 2004.
  • Neely CF, Haile D, Matot I: Tone dependent responses of 5-hydroxytryptamine in the Feline pulmonary vascular bed are mediated by two different 5-hydroxytryptamine receptors. J Pharmacol Exp Ther. 264:1315-26, 1992.
  • Morecroft I, MacLean MR:5- hydroxytryptamine receptors mediating vasoconstriction and vasodilation in perinatal and adult rabbit small pulmonary arteries. Br J Pharmacol. 125:69-78, 1998.
  • Saxena PR, Verdouw PD: 5-Carboxamide tryptamine, a compound with high affinity for 5-hydroxytryptamine1 binding sites, dilates arterioles and constricts arteriovenous anastomoses. Br J Pharmacol. 84: 533-44, 1985.
  • Verdouw PD, Jennewein HM, Heiligers J, Duncker DJ, Saxena PR: Redistribution of carotid artery blood flow by 5-HT: effects of the 5-HT2 receptor antagonists ketanserin and Wal 1307. Eur J Pharmacol. 102: 499-509, 1984.
  • Lippton HL, Hao Q, Hyman A: L-NAME enhances pulmonary vasoconstriction without inhibiting EDRF-dependent vasodilation. J Appl Physiol. 73:2432-9, 1992.
  • Yildiz O, Tuncer M: 5HT1-like and 5HT2A receptors mediate 5-hydroxytryptamine- induced contraction of rabit isolated mesenteric artery. Naunyn-Schmiedebergs-Arch- Pharmacol. 352:127-131, 1995.
  • Engler RL: Lidoflazine in the treatment of comatose survivors of cardiac arrest [letter]. N Engl J Med. 325:1046-7, 1991.
  • Turker MN, Turker RK: Analgesic action of lidoflazine (R 7904). Eur J Pharmacol. 11: 90- 5, 1970.
  • Emori T, Hirata Y, Kanno K, Ohta K, Eguchi S, Imai T, Shichiri M, Marumo F: Endothelin-3 stimulates production of endothelium-derived nitric oxide via phosphoinositide breakdown. Biochem Biophys Res Commun. 174:228-235, 1991.
  • Haluzik M, Nedvidkova J, Schreiber V: Methylene blue an endocrine modulator. Sb Lek. 96:319-22, 1995.
  • Golino P, Piscione F, Willerson JT, Cappelli Bigazzi M, Focaccio A, Villari B, Indolfi C, Russolillo E, Condorelli M, Chiariello M: Divergent effects of serotonin on coronary- artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med. 324:641-8, 1991.
  • Hadj Kaddour K, Michel A, Chevillard C: Endothelin-1 and Endothelin-3 relaks isolated guinea pig trechea through different mechanisms. J Cardiovasc Pharmocol. Suppl 3:115-6, 1995.

Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi.

Yıl 2007, Cilt: 9 Sayı: 1, 27 - 35, 01.03.2007

Öz

Bu çalismada izole perfüze siçan akciger preperatinda serotoninin etkileri, serotonin-lidoflazin etkilesmesi ve altta yatan olasi mekanizmalarin ortaya çikarilmasi amaçlanmistir. Deneylerde serotonin yanitlarina karsi nükleozid tranportunu inhibe ederek endojen adenozini arttiran ve kalsiyum kanal blokeri olan lidoflazin, adenozin antagonisti teofilin, guanilat -siklaz inhibitörü metilen-mavisi (MM) ve siproheptadin kullanilmistir. Sonuçlarimiz serotoninin pulmoner arter perfüzyon basincinda doza -bagimli bifazik bir artma yaptigini gösterdi. Erken pressör yanit faz-I (F1) ve bundan sonraki düsmeyi izleyen pressör yanit faz-II (F2) olarak isimlendirildi. Lidoflazin, serotonine bagli F1’de dozla orantili bir artma ve F2’de inhibisyon olusturdugu belirlendi. Siproheptadin ise; serotoninin hem F1‘de hemde F2 yanitlarinda doza bagli inhibisyon olusturdu. Deneylerimizde lidoflazinin F1’de yaptigi potansiyalizasyonun siproheptadin ile anlamli bir sekilde antagonize edildigi görüldü. Lidoflazin-siproheptadin kombinasyonu, serotoninin F1 yanitlarini anlamli bir sekilde deprese etti. Lidoflazinin F2’ye inhibitör etkisi siproheptadin ile potansiyelize edildi. Teofilin F1’de anlamli olmayan bir artma olusturdu ve lidoflazinin F1 yanitlarinda yaptigi potansiyalizasyonu antagonize etti; F2’de ise anlamli olmayan bir azalmaya neden oldu ve lidoflazinin bu faza olan inhibitör etkisini güçlendirdi. MM hem F1 hem de F2 de inhibitör etki yapti ve lidoflazinin F1 fazinda neden oldugu artmayi engelledi. Serotonin yanitlarinin bifazik olmasi siçan pulmoner vaskuler sistemde çesitli serotonin reseptörlerin bulundugunu düsündürmektedir. Lidoflazinin F1 arttirmasi, adenozini arttirmasi yoluyla olabilir. F2’nin deprese edilmesi, lidoflazinin F2’yi olusturan serotonin reseptörleri üzerine muhtemelen nonspesifik antagonistik etkisi oldugunu telkin etmektedir. Siproheptadinin F2 üzerine olan inhibitör etkisinin F1’den daha güçlü olmasi, F1’in F2’den daha farkli bir reseptör araciligi ile olusabilecegini düsündürmektedir. Teofilinin F1 yanitlarinda lidoflazinin yaptigi artisi inhibe etmesi, bu yanitta adenozinin rolü oldugunu akla getirmektedir. MM ile yapilan deneyler serotonin yanitlarinda damar endotelinin de önemli bir rol oynadigini göstermektedir

Kaynakça

  • Süzer Ö: Serotonin, serotonin reseptörlerinin baslica etki yerleri ve fonksiyonlari: Süzer Farmakoloji. 3. baski: Istanbul. Klinisyen Tip Kitabevleri. 150-4, 2005.
  • Ridley JM, Dooley PC, Milnes JT, Witchel HJ, Hancox JC: Lidoflazine is a high affinity blocker of the HERG K(+) channel. J Mol Cell Cardiol. 36:701-5, 2004.
  • Hugtenburg JG, Mathy MJ, Boddeke HW, Beckeringh JJ, Van Zwieten PA: Differences between negative inotropic and vasodilator effects of calcium antagonists acting on extra and intracellular calcium movements in rat and guinea-pig cardiac preparations. Naunyn Schmiedebergs Arch Pharmacol. 340:567-75, 1989.
  • Barry WH, Horowitz JD, Smith TW : Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells. Br J Pharmacol. 85:51-9, 1985.
  • Boddeke HW, Wilffert B, Heynis JB, Van de Haar Keuken V, Jonkman FA, Van Zwieten PA: A comparison of the cardiac and vasodilatory effects of some calcium entry blockers in perfused isolated guinea-pig hearts. Arch Int Pharmacodyn Ther. 288:175-85, 1987.
  • Engler RL, Gruber HE: Adenosine: An autocoid, in Fozzard HA, Haber E, Jennings RB, et al (eds): The Heart: An Cardiovascular System, New York, Raven Press. pp: 1745- 1764, 1992.
  • Chang-Chun C, Masuda M, Szabo Z, Szerafin T, Szecsi J, Van Belle H, Flameng W: Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping. J Thorac Cardiovasc Surg. 104:1602-9, 1992.
  • Bakhle YS, Reynard AM, Vane JR: Metabolism of the angiotensins in isolated perfused tissues. Nature. 222:956-9, 1969.
  • Burkhalter A, Julius D, Frick OL: Serotonin. Pharmacolgy (edited by Katzung BG) Appleton & Lang. (USA) sixthedition 262-266, 1995.
  • Cohen RA, Shepherd JT, Vanhoutte PM: Inhibitory role of the endothelium in the response of isolated coronary arteries to platelets. Science. 221:273-4, 1983.
  • Humphrey PP, Feniuk W, Perren MJ, Connor HE, Oxford AW, Coates LH, Butina D: GR43175, a selective agonist for the 5-HT1- like receptor in dog isolated saphenous vein. Br J Pharmacol. 94:1123-32, 1988.
  • Küçükhüseyin C: Purinrjik sinir sistemi. Cerrahpasa Tip Fak. Derg. 22:161-170, 1991.
  • Van Zwieten PA: Conclusions on the position of uradipil. Am. J. Cardiol. 64:38-39D, 1989.
  • Eder V, Gautier M, Boissiere J, Girardin C, Rebocho M, Bonnet P. Gamma irradiation induces acetylcholine-evoked, endothelium- independent relaxation and activates K- channels of isolated pulmonary artery of rats. Int J Radiat Oncol Biol Phys. 60:1530-7, 2004.
  • Neely CF, Haile D, Matot I: Tone dependent responses of 5-hydroxytryptamine in the Feline pulmonary vascular bed are mediated by two different 5-hydroxytryptamine receptors. J Pharmacol Exp Ther. 264:1315-26, 1992.
  • Morecroft I, MacLean MR:5- hydroxytryptamine receptors mediating vasoconstriction and vasodilation in perinatal and adult rabbit small pulmonary arteries. Br J Pharmacol. 125:69-78, 1998.
  • Saxena PR, Verdouw PD: 5-Carboxamide tryptamine, a compound with high affinity for 5-hydroxytryptamine1 binding sites, dilates arterioles and constricts arteriovenous anastomoses. Br J Pharmacol. 84: 533-44, 1985.
  • Verdouw PD, Jennewein HM, Heiligers J, Duncker DJ, Saxena PR: Redistribution of carotid artery blood flow by 5-HT: effects of the 5-HT2 receptor antagonists ketanserin and Wal 1307. Eur J Pharmacol. 102: 499-509, 1984.
  • Lippton HL, Hao Q, Hyman A: L-NAME enhances pulmonary vasoconstriction without inhibiting EDRF-dependent vasodilation. J Appl Physiol. 73:2432-9, 1992.
  • Yildiz O, Tuncer M: 5HT1-like and 5HT2A receptors mediate 5-hydroxytryptamine- induced contraction of rabit isolated mesenteric artery. Naunyn-Schmiedebergs-Arch- Pharmacol. 352:127-131, 1995.
  • Engler RL: Lidoflazine in the treatment of comatose survivors of cardiac arrest [letter]. N Engl J Med. 325:1046-7, 1991.
  • Turker MN, Turker RK: Analgesic action of lidoflazine (R 7904). Eur J Pharmacol. 11: 90- 5, 1970.
  • Emori T, Hirata Y, Kanno K, Ohta K, Eguchi S, Imai T, Shichiri M, Marumo F: Endothelin-3 stimulates production of endothelium-derived nitric oxide via phosphoinositide breakdown. Biochem Biophys Res Commun. 174:228-235, 1991.
  • Haluzik M, Nedvidkova J, Schreiber V: Methylene blue an endocrine modulator. Sb Lek. 96:319-22, 1995.
  • Golino P, Piscione F, Willerson JT, Cappelli Bigazzi M, Focaccio A, Villari B, Indolfi C, Russolillo E, Condorelli M, Chiariello M: Divergent effects of serotonin on coronary- artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med. 324:641-8, 1991.
  • Hadj Kaddour K, Michel A, Chevillard C: Endothelin-1 and Endothelin-3 relaks isolated guinea pig trechea through different mechanisms. J Cardiovasc Pharmocol. Suppl 3:115-6, 1995.
Toplam 26 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Research Article
Yazarlar

Coskun Sılan Bu kişi benim

Cihat Küçükhüseyın Bu kişi benim

Yayımlanma Tarihi 1 Mart 2007
Yayımlandığı Sayı Yıl 2007 Cilt: 9 Sayı: 1

Kaynak Göster

APA Sılan, C., & Küçükhüseyın, C. (2007). Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi. Duzce Medical Journal, 9(1), 27-35.
AMA Sılan C, Küçükhüseyın C. Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi. Duzce Med J. Mart 2007;9(1):27-35.
Chicago Sılan, Coskun, ve Cihat Küçükhüseyın. “Izole siçan Pulmoner Damar Yataginda Serotoninin Neden Oldugu Bifazik Etkinin Mekanizmasi”. Duzce Medical Journal 9, sy. 1 (Mart 2007): 27-35.
EndNote Sılan C, Küçükhüseyın C (01 Mart 2007) Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi. Duzce Medical Journal 9 1 27–35.
IEEE C. Sılan ve C. Küçükhüseyın, “Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi”., Duzce Med J, c. 9, sy. 1, ss. 27–35, 2007.
ISNAD Sılan, Coskun - Küçükhüseyın, Cihat. “Izole siçan Pulmoner Damar Yataginda Serotoninin Neden Oldugu Bifazik Etkinin Mekanizmasi”. Duzce Medical Journal 9/1 (Mart 2007), 27-35.
JAMA Sılan C, Küçükhüseyın C. Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi. Duzce Med J. 2007;9:27–35.
MLA Sılan, Coskun ve Cihat Küçükhüseyın. “Izole siçan Pulmoner Damar Yataginda Serotoninin Neden Oldugu Bifazik Etkinin Mekanizmasi”. Duzce Medical Journal, c. 9, sy. 1, 2007, ss. 27-35.
Vancouver Sılan C, Küçükhüseyın C. Izole siçan pulmoner damar yataginda serotoninin neden oldugu bifazik etkinin mekanizmasi. Duzce Med J. 2007;9(1):27-35.
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