[Substance P and its receptors are involved in the effect of histamine H3 receptor agonist, IMETIT on nasal allergic symptoms in guinea pigs].
OBJECTIVE
To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R) mRNA in AR model in guinea pigs.


METHODS
Guinea pigs were divided randomly into 4 groups: AR group (group A), IMETIT group (group B), Loratadine group (group C) and IMETIT+Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13.0 software.


RESULTS
In Group B, the mean (x ± s) number of sneeze [(15.0 ± 1.3) times], scratching nose [(16.5 ± 2.3) times] and respiratory frequency [(76.3 ± 4.1) times/min] were significantly improved than those in group A [(23.5 ± 2.6) times, (26.1 ± 4.1) times and (66.5 ± 5.8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP-positive cells [(11.6 ± 3.6)/HP] and SP-R mRNA expression (0.64 ± 0.04) in group B were reduced significantly compared to group A [(27.1 ± 9.7)/HP, (0.83 ± 0.03), P value were 0.000, 0.000, respectively]. Sneeze [(10.0 ± 2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [(90.0 ± 5.0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0.002 and 0.000, respectively). SP-positive cells [(2.0 ± 1.7)/HP] and SP-R mRNA expression (0.52 ± 0.06) in Group D compared with group B were also significantly reduced (P value were 0.012 and 0.000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11.59, 8.28, 5.61, 5.48, 6.50, respectively, P value were 0.002, 0.008, 0.025, 0.027, 0.017).


CONCLUSIONS
IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-R mRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.
Department of Otorhinolaryngology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. jssunguangming@126.com
Guang-ming
GM
Sun
Xu-dong
XD
Yang
Xue-gu
XG
Xu
Pei-hua
PH
Li
Wen
W
Liu
Li-juan
LJ
Pan
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D017442:Histamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D017336:Loratadine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000378:metabolism*; D013373:Substance P / Q000235:genetics / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D017442:Histamine Agonists; D007093:Imidazoles; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D013373:Substance P; C077430:imetit; D017336:Loratadine; D013890:Thiourea