Korean J Physiol Pharmacol.  2014 Feb;18(1):41-46. 10.4196/kjpp.2014.18.1.41.

The Modulatory Role of Spinally Located Histamine Receptors in the Regulation of the Blood Glucose Level in D-Glucose-Fed Mice

• Sim YB
• Park SH
• Kim SS
• Kim CH
• Kim SJ
• Lim SM
• Jung JS
• Ryu OH
• Choi MG
• Suh HW

• KMID: 2285489
• DOI: http://doi.org/10.4196/kjpp.2014.18.1.41

Abstract

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (alpha-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with alpha-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, alpha-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

Keyword

Blood glucose; D-glucose; Histamine receptors; Spinal cord

MeSH Terms

Animals
Blood Glucose*
Cetirizine
Dimaprit
Down-Regulation
Glucose
Histamine*
Mice*
Mice, Inbred ICR
Ranitidine
Receptors, Histamine H2
Receptors, Histamine H3
Receptors, Histamine*
Spinal Cord
Up-Regulation
Blood Glucose
Cetirizine
Dimaprit
Glucose
Histamine
Ranitidine
Receptors, Histamine
Receptors, Histamine H2
Receptors, Histamine H3

Figure

• 

  Fig. 1 Effect of 2-pyridylethylamine or cetirizine administered i.t. on the blood glucose level. Mice were intrathecally (i.t.) administered with 2-pyridylethylamine (from 0.1 to 1 µg) (A) or cetirizine (from 0.05 to 0.5 µg) (B). The 16 h fasted mice were pretreated i.t. with 2-pyridylethylamine (C) or cetirizine (D) for 10 min and then, D-glucose (2 g/kg body weight) administered orally once. The blood glucose level was measured at 30, 60 and 120 min after i.t. or oral administration. The blood was collected from tail-vein. The vertical bars indicate the standard error of mean. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test (C and D: **p<0.01, ***p<0.005; compared to D-Glucose+Saline group). The number of animals used for each group was 8~10.

• 

  Fig. 2 Effect of dimaprit or ranitidine administered i.t. on the blood glucose level. Mice were intrathecally (i.t.) administered with dimaprit (from 1 to 10 µg) (A) or ranitidine (from 5 to 20 µg) (B). The 16 h fasted mice were pretreated i.t. with dimaprit (C) or ranitidine (D) for 10 min and then, D-glucose (2 g/kg body weight) administered orally once. The blood glucose level was measured at 30, 60 and 120 min after i.t. or oral administration. The blood was collected from tail-vein. The vertical bars indicate the standard error of mean. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test (C: **p<0.01, ***p<0.005; compared to D-Glucose+Saline group). The number of animals used for each group was 8~10.

• 

  Fig. 3 Effect of α-methylhistamine or carcinine administered i.t. on the blood glucose level. Mice were intrathecally (i.t.) administered with α-methylhistamine (0.5 to 5 µg) (A) or carcinine (from 1 to 10 µg) (B). The 16 h fasted mice were pretreated i.t. with α-methylhistamine (C) or carcinine (D) for 10 min and then, D-glucose (2 g/kg body weight) administered orally once. The blood glucose level was measured at 30, 60 and 120 min after i.t. or oral administration. The blood was collected from tail-vein. The vertical bars indicate the standard error of mean. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test (A: **p<0.01; compared to saline group, C and D: *p<0.05; compared to D-Glucose+Saline group). The number of animals used for each group was 8~10.

• 

  Fig. 4 Effect of VUF 8430 or JNJ 7777120 administered i.t. on the blood glucose level. Mice were intrathecally (i.t.) administered with VUF 8430 (from 0.5 to 5 µg) (A) or JNJ 7777120 (from 1 to 10 µg) (B). The 16 h fasted mice were pretreated i.t. with VUF 8430 (C) or JNJ 7777120 (D) for 10 min and then, D-glucose (2 g/kg body weight) administered orally once. The blood glucose level was measured at 30, 60 and 120 min after i.t. or oral administration. The blood was collected from tail-vein. The vertical bars indicate the standard error of mean. Each quantified result was analyzed by one-way ANOVA with a Bonferroni post hoc test (D: *p<0.05; compared to D-Glucose +PEC group). The number of animals used for each group was 8~10.

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