In vivo comparative immunotoxic study of histamine receptors (H1R, H2R, H3R and H4R)-agonist

Year 2010, Volume: 15 Issue: 2, 48 - 56, 15.01.2013

Trivendra Tripathi Mohammad Shahid Adil Raza Haris M. Khan Mashiatullah Siddiqui Abida Malik Rahat Ali Khan

Abstract

Abstract. Accumulating evidences have highlighted histamine and histamine receptors (HRs)-antagonists’ role in immunomodulation. However, the roles of HRs-agonists are still unclear. The present study was therefore designed to delineate the comparative immunotoxic roles of H1-H4-agonist on antibody generation profile in rabbit model. The cohort comprised of seven groups (Group-I negative control, group-II positive control and group-III-VII HRs-agonist-treated) containing 18 (9 male and 9 female) rabbits each. Group-I and group-II received vehicle (sterile distilled water, 1mlkg^-1×b.i.d.) intramuscularly. Groups-III-VII (HRs-agonist-treated) received subcutaneous histamine (100µgkg^-1) and H1-agonist (HTMT), H2-agonist (amthamine), H3-agonist (R-[-]-α-methylhistamine) and H4-agonist (clobenpropit) each in a dose of 10µgkg^-1, respectively, b.i.d. for 10 days (starting from day 1). Groups-II-VII were subsequently immunized with intravenous injection of SRBC at day 3. The estimation of serum immunoglobulins (Ig), IgM and IgG were done by ELISA, and observed at day 0 (pre-immunization) and day 7, 14, 21, 28 and 58 (post-immunization). Results showed that histamine and HRs-agonist could influence a detectable antibody response to SRBC as early as day 7-postimmunization (post-I), which lasted until day 58- post-I. All the results were found statistically significant (p<0.05). To conclude, our results provide evidences that HTMT, amthamine and clobenpropit (H1-, H2- and H4-agonist, respectively) have important role in modulation of antibody generation by enhancing production level, in which HTMT have dominant role, while amthamine and clobenpropit play similar role. Conversely, R-[-]-α-methylhistamine (H3-agonist) have dominant inhibitory role on antibody production.

Key words: Histamine, histamine receptors, agonists, immunomodulation, antibody generation, immunotoxic

Keywords

Histamine, histamine receptors, agonists, immunomodulation, antibody generation, immunotoxic

References

• Shahid M, Tripathi T, Sobia F, et al. Histamine, histamine receptors, and their role in immunomodulation: an updated systematic review. Open Immunol J 2009; 2: 9-41.
• Falus A, Hargita H, Eszter L, et al. Paracrine and autocrine interactions in melanoma: histamine is a relevant player in local regulation. Trends Immunol 2001; 22: 648-652.
• Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nature Rev Drug Dis 2008; 7: 41-53.
• Huang JF, Thurmond RL. The New Biology of Histamine Receptors. Curr Allergy Asthma Rep 2008; 8: 21-27.
• Ma RZ, Gao J, Meeker ND, et al. Identification of Bphs, an autoimmune disease locus, as histamine receptor H1. Science 2002; 297: 620-623.
• Quintana FJ, Buzas E, Prohászka Z, et al. Knock-out of the histidine decarboxylase gene modifies the repertoire of natural autoantibodies. J Autoimmun 2004; 22: 297-305.
• Jutel M, Watanabe T, Klunker S, et al. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 2001; 413: 420-425.
• Lim HD, van Rijn RM, Ling P, et al. Evaluation of Histamine H1-, H2-, and H3-Receptor Ligands at the Human Histamine H4 Receptor: Identification of 4-Methylhistamine as the First Potent and Selective H4 Receptor Agonist. J Pharmacol Exp Ther 2005; 314: 1310-1321.
• Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R. Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 2001; 60: 1133-1142.
• Leurs R, Smit MJ, Menge WM, Timmerman H. Pharmacological characterization of the human histamine H2 receptor stably expressed in Chinese hamster ovary cells. Br J Pharmacol 1994; 112: 847- 854.
• Hill SJ, Chazot P, Fukui H, et al. Histamine receptors. 2008. Available at: IUPHAR database (IUPHAR-DB), http://www.iuphar- db.org/PRODDATABASE/FamilyMenuForward?fa milyId=33. Accessed May 04, 2010.
• Stark H. Histamine Receptors. Biotrends Rev 2007; 1: 2-9. Available from: http: //www.biotrend.com.
• Ling P, Ngo K, Nguyen S, et al. Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 2004; 142: 161-171.
• Tripathi T, Khan AA, Shahid M, et al. Hepatotoxicity due to Histamine Trifluoro-Methyl Toluidide, Amthamine, R-(-)-α-methylhistamine and Clobenpropit (H1R-H4R-Agonists, Respectively) in Rabbit Experimental Model. Am Med J 2010; 1: 1- 7.
• Dagli M, Goksu N, Eryilmaz A, et al. Expression of histamine receptors (H1, H2, and H3) in the rabbit endolymphatic sac: an immunohistochemical study. Am J Otolaryngol 2008; 29: 20-23.
• Ercan ZS, Türker RK. Histamine Receptors in the Isolated Rat Stomach Fundus and Rabbit Aortic Strips. Pharmacology 1977; 15: 118-126.
• Dey SK, Villanueva C, Abdou NI. Histamine receptors on rabbit blastocyst and endometrial cell membranes. Nature 1979; 278: 648-649.
• Tayo FM, Bevan JA. Pharmacological characterization of histamine receptors in the rabbit renal artery. Eur J Pharmacol 1986; 121: 129-33.
• Gutzmer R, Mommert S, Gschwandtner M, et al. The histamine H4 receptor is functionally expressed on TH2 cells. J Allergy Clin Immunol 2009; 123: 619-625.
• Tsuru H, Kohno S, Iwata M, Shigei T. Characterization of histamine receptors in isolated rabbit veins. J Pharmacol Exp Ther 1987; 243: 696- 702.
• Champion HC, Bivalacqua TJ, Lambert DG, Abassi RA, Kadowitz PJ. Analysis of vasoconstrictor responses to histamine in the hindlimb vascular bed of the rabbit. Am J Physiol Regul Integr Comp Physiol 1999; 277: R1179-R1187.
• Moharana AK, Bhattacharya SK, Mediratta PK, Sharma KK. Possible role of histamine receptors in the central regulation of immune responses. Indian J Physiol Pharmacol 2000; 44: 153-160.
• Tripathi T, Shahid M, Khan HM, et al. Effect of histamine on antibody generation profile in vivo. Global J Applied Physiology Allied Sciences 2009; 1: 26-31.
• Tripathi T, Shahid M, Khan HM, et al. Dose- dependent effect of histamine on antibody generation in vivo. As Pac J Tropic Med 2010; 3: 112-116.
• Franzl RE. The primary immune response in mice III. Retention of sheep red blood cell immunogens by the spleen and liver. Infection Immunity 1972; 6: 469-482.
• Doumal E. Standard method of clinical chemistry. Publ Academy Press 1972; pp 5-88.
• Koganei A, Tsuchiya T, Samura K, Nishikibe M. Use of whole sheep red blood cells in ELISA to assess immunosuppression in vivo. J Immunotoxicol 2007; 4: 77-82.
• Tripathi T, Shahid M, Siddiqui MU, Khan RA. Role and immunomodulatory profile of histamine receptors by H1 and H2 antagonists. 2008. Available at Nature Precedings: http://precedings.nature.com/documents/1547/versio n/1. Accessed May 04, 2010.
• Putman E, van Loveren H, Bode G, et al. Assessment of the immunotoxic potential of human pharmaceuticals: A workshop report. Drug Inform J 2002; 36: 417-427.
• Akdis CA, Simons FER. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol 2006; 533: 69-76.
• Banu Y, Watanabe T. Augmentation of antigen receptor-mediated responses by histamine H1 receptor signaling. J Exp Med 1999; 189: 673-682.