Effects of histamine HlR-H4R-agonist on the airway epithelium of rabbits

Objective:To explore the exact role of histamine receptors in respiratory system.Methods: The cohort comprised of six groups(group I control and groupⅡ—Ⅳtreated) containing five rabbits in each group.Control-group received vehicle(sterile distilled water) and treated groups received subcutaneous histamine(100μg/kg,b.i.d.),and H1R-agonist(HTMT),H2R-agonist (amthamine),H3R-agonist(R-(-)-α-methylhistamine) and H4R-agonist(clobenpropit) each in a dose of 10μg/kg,b.i.d.for 30 subsequent days.After completion of treatment,animals were euthanized and perfused with 10% buffered formalin.Small tissue blocks of trachea and lungs were processed for paraffin embedding.Observations were recorded in sample photomicrographs taken from 10μm thick.Haematoxylin and eosin stained sections.Results:It was observed that trachea and bronchi from histamine,H1R and H4R groups had only patches of hyperplastic and hypertrophied epithelium and in general,cells in the affected region were taller heaped up. The bronchiolar epithelia from all treated groups showed hypertrophy and hyperplasia throughout with most of the cells having rounded profile and appeared to bud out from the basal cells. Conclusions:It is concluded that histamine receptors on induction via its specific agonist can induce hypertrophy,hyperplasia of respiratory tract epithelia suggesting its role akin to growth stimulating factor and warranting further long-term study.

In vivo immunomodulatory profile of histamine receptors(H1,H2,H3 and H4):a comparative antagonists study

Objective:To delineate the comparative immunomodulatory roles of H1R-H4R in antibody generation profile in rabbit model.Methods:The cohort comprised of eight groups containing 18(9 male and 9 female) rabbits in each group.GroupⅠremained non-immunized and received only vehicle(sterile distilled water,1 mL/kg×b.i.d.) intramuscularly.GroupⅡreceived vehicle (1 mL/kg×b.i.d.) while GroupsⅢ-Ⅶ(drugs-treated) received subcutaneous histamine (100μg/kg×b.i.d.),and intramuscular H1R-antagonist(pheniramine,10 mg/kg×b.i.d.), H2R-antagonist(ranitidine,10 mg/kg×b.i.d.),H3R-antagonist(iodophenpropit,1μg/kg×b.i.d.) and H4R-antagonist(JNJ 7777120,10μg/kg×b.i.d.),and GroupⅧDMSO(1 mL/kg×b.i.d.),respectively for 10 days(starting from day 1).They were subsequendy immunized with intravenous injection of sheep red blood cells(SRBC) at day 3.The estimation of serum Igs,IgM and IgG were done by ELISA,and observed at day 0(pre-immunization),and 7,14,21,28 and 58(post-immunization).Results:It was shown that histamine and HRs-antagonists could influence a detectable antibody response to SRBC as early as day 7-post-immunization(post-Ⅰ), which lasted until day 58 post-Ⅰ.The results were found statistically significant(P【0.05,). Conclusions:This study suggests that histamine receptors play important roles in modulation of antibody generation in which H1R,H2R and H4R have immunosuppressive roles and conversely, H3R playes an immune enhancing role.The findings of this study may have clinical significance and provide the baseline information for future study.