The Role of Nitric Oxide on Histamine H3 Receptors Mediated Rat Gastric Fundus Contractile Responses

Abstract

Objective: Determining the possible effects of nitric oxide (NO) on histamine H3 receptor mediated contractile responses on gastric fundus smooth muscle. Material and Methods: Isolated rat gastric fundus preparations were mounted on isolated organ bath. Histamine receptor agonist and antagonists were added to the bath solution, then the electrical field stimulation (EFS) induced contractile responses were evaluated. Results: In our study groups after blocking the histamine receptors H1 by Pyrilamine (10-6м) and H2 by Famotidine (10-6м); contractile responses given to the histamine H3 receptor agonist (R)-α-methylhistamine (RAMH) on (10-8- 10-5м ) molar concentrations were observed. The same protochol was carried out to view the changes in the presence of NO precursore L-arginin (L-Arg)(10-4м, NO synthase inhibitor L-nitro-arginine-methyl ester (L-NAME) (10-4м) and combination of them. Conclusion: It was concluded that there were no significant effect of NO on the contractile responses of histamine receptors since the presence of NO precursore L-Arg (10-4м) and NO synthase inhibitor L-NAME (10-4м ) and combination of them made no differences in the contractile responses. Key words: Histamine H3 receptor, Nitric oxide, Gastric fundus (R)-Α-Methylhistamine, Contractility, Electrical field stimulation.

Keywords

• Histamine H3 receptor, Nitric oxide, Gastric fundus (R)-Α-Methylhistamine, Contractility, Electrical field stimulation.

Sıçan Mide Fundus Şeritlerinde Histamin H3 Reseptörleri Aracılı Kasılma Yanıtları Üzerine Nitrik Oksitin Rolü

Öz

Amaç: Mide fundus düz kasında histamin H3 reseptör aracılı kasılmaları üzerine nitrik oksitin (NO) olası rolünü gözlemlemektir. Gereç ve Yöntem: İzole edilen sıçan mide fundus preparatları organ banyosuna asıldıktan sonra ortama histamin agonist ve antagonistleri ilave edilerek elektriksel alan stimülasyonuna (EFS) verdikleri kasılma yanıtları incelendi. Bulgular: Çalışma gruplarımızda histamin H1, H2 reseptörleri sırasıyla H1 reseptör blokörü Pirilamin (10-6м) ve H2 reseptör blokörü (10-6м) Famotidin ile bloke ettikten sonra elektriksel uyarı aracılığı ile elde edilen kasılma yanıtlarına H3 reseptör agonisti (R)-α-metilhistamin'in (RAMH) (10-8- 10-5 м ) molar derişimlerinin etkileri kümülatif olarak incelendi. Daha sonra NO ile olası bir etkileşimin gözlenmesi amacıyla farklı serilerde ortamda NO prekürsörü L-arginin (L-Arg) (10-4м) ve NO sentaz inhibitörü L-nitro-arginine-methyl ester (L-NAME) (10-4м) ve kombinasyonlarının bulunduğu halde aynı prosedür tekrarlandı, ancak anlamlı bir farklılık ile karşılaşılmadı. Sonuç: Nitrik oksidin histamin reseptörleri aracılı kasılma yanıtları üzerine herhangi bir etkisinin bulunmadığı sonucuna varıldı. Anahtar kelimeler: Histamin H3 reseptör, Nitrik oksit, İleum, (R)-α-Metilhistamin, Kasılma, Elektriksel alan stimülasyonu.

Anahtar Kelimeler

• Histamin H3 reseptör, Nitrik oksit, İleum, (R)-α-Metilhistamin, Kasılma, Elektriksel alan stimülasyonu.

Kaynakça

1. Levi R, Rubin LE and Gross SS. Histamine in cardiovascular function and dysfunction: Recent developments. Handbk Exp Pharmacol 1991; 97: 347–83.
2. Arrang JM, et al. Highly potent and selective ligands for histamine H3-receptors. Nature 327: 117–23.
3. Timmerman H. Histamine H3 ligands: Just pharmacological tools or potential therapeutic agents? J Med Chem 1990; 33: 4–11.
4. Göthert M, Garbarg M, Hey JA, Schlicker E, Schwartz JC and Levi R. New aspects of the role of histamine in cardiovascular function: Identification, characterization and potential pathophysiological importance of H3 receptors. Can J Physiol Pharmacol 1995; 73:558–64.
5. Bertaccini G, Morini G, Coruzzi G, Schunack W. Histamine H3 receptors in the guinea pig ileum: evidence for a postjunctional location. J Physiol Paris. 2000; 94:1-4.
6. EA-Kim L, Javellaud J and Oudart N. Endothelium-dependent relaxation of rabbit middle cerebral artery to a histamine H3 agonist is reduced by inhibitors of nitric oxide and prostacyclin synthesis. Br J Pharmacol 1992; 105:103–6.
7. Martinez AC, Novella S, Raposo R, et al. Histamine receptors in isolated bovine oviductal arteries. Eur J Pharmacol 1997; 326:163–73.
8. Oike M, Kitamura K and Kuriyama H. Histamine H3-receptor activation augments voltage-dependent Ca2+ current via GTP hydrolysis in rabbit saphenous artery. J Physiol 1992; 448, pp. 133–52.

9. Ambache N and Aboo Zar M. An inhibitory action of histamine on the guinea-pig ileum. Br J Pharmacol, 1970; 38:229-40.
10. Arrang JM, Garnarb M and Schwartz JC. Autoinhibition of brain histamine release by a novel class (H3) of histamine receptors. Nature 1983; 327:117-23.
11. Schlicker E, Betz R and Gothert M. Histamine H3-receptor-mediated inhibition of serotonin release in the rat brain cortex. Naunyn-Schmiedebergs Arch Pharmacol 1988; 337:588-90.
12. Ishikawa S and Sperelakis N. A novel class (H3) of histamine receptors on perivasculer nerve terminals. Nature 1987; 327:158-60.
13. Hew RWS and Hodgkinson CR. Characterization of histamine H3-receptors in guinea pig ileum with H3-selective ligands. Br J Pharmacol, 1990; 101:621-4.
14. Champion HC and Kadowitz. PJ. R-(α)-methyl-histamine has nitric oxide-mediated vasodilator activity in the mesenteric vascular bed of the cat. European Journal of Pharmacology 1998; 343( 2-3):209-16.
15. By the staff of department of pharmacology, University of Edinburg, Pharmacological experiments on isolated preparations. Secon edition: 1970: 88-91.
16. Bado A, Hervatin F and Lewin MJ. Pharmacological evidence for histamine H3 receptor in the control of gastric acid secretion in cats. Am J Physiol 1991; 260:631– 5.
17. Kayaalp SO.: Rasyonel tedavi yönünden tıbbi farmakoloji, Onuncu baskı, 2002: sayfa : 979-80.
18. Kayaalp SO.: Rasyonel tedavi yönünden tıbbi farmakoloji, Onuncu baskı, 2002: sayfa: 549-53.
19. Franco R, Costa M and Furness JB. Evidence for the release of endogenous substance P from intestinal nerves. Naunyn-Schiedeberg’s Arch Pharmacol 1979; 306:195-201.
20. Dikshit BB. Acetylcholine formation by tissues. Exp Physiol, 1938; 28:243-51.
21. Patel NM, Goyal RK and Verma SC. Histaminergic H1 ve H2 excitatory receptors in the guinea pig uterus and taenia coli. Can J Physiol Pharmacol 1980; 58: 1500-3.
22. Barker LA and Ebersole BJ. Histamine H2 receptors on guinea pig ileum myenteric plexus neurons mediate the release of conractile agents. J Pharmacol Exp Ther 1982; 221:69-75.
23. Bertaccini G. Amines: Histamine in mediators and drugs in gastrointestinal motility, ed. By G. Bertaccini, Handbook Experimental Pharmacology, 1982: 59: 201-18.
24. Coruzzi G, Poli E and Bertaccini G. Histamine receptors in isolated guinea pig duodenal muscle: H3 receptors inhibit cholinergic neurotransmission. J Pharmacol Exp Ther 1991; 258:325-31.
25. Bertaccini G, Zappia L. Histamine receptors in the guinea pig duodenum. J Pharmacol 1981; 33:590-3.
26. Ichinose M, Barnes PJ. Inhibitory histamine H3 receptors on cholinergic nerves in human airways. Eur J Pharmacol 1989; 163:383-6.
27. V. Ballabeni , F. Calcina , M. Bosetti et al. Different Role of the Histamine H3 Receptor in Vagal-, Betanechol-, Pentagastrin-induced Gastric Acid Secretion in Anaesthetized Rats. Scandinavian Journal of Gastroenterology 2002; 37(7):754-8.
28. Schaefer U, Schneider A, Rudroff C, Neugebauer E. Nitric oxide mediates histamine induced down-regulation of H2 receptor mRNA and internalization of the receptor protein (R1). Cell Mol Life Sci 2003; Sep;60(9):1968-81.