Role of 5-HT2 receptors family in the allergy-induced increased aorta contractile responses to 5-HT

Abstract

Asthma poses an increased risk for cardiovascular disorders, suggesting that allergy, which is an underlying process in asthma, causes atypical functioning of organs other than lungs. In a previous study in a guinea pig asthma model, we concluded that allergic sensitization increased aorta contractile responses to 5-HT. To further characterize these responses, here we explored the role of the 5-HT2 receptors family. We found that TCB-2 (5-HT2A agonist) and WAY161503 (5-HT2C agonist) induced aorta contractions resembling those elicited by 5-HT but less intense (~43 % and ~25 %, respectively). In these experiments, aortas from sensitized guinea pigs showed increased contractions to TCB-2, but not to WAY161503. In turn, MDL 100907 (5-HT2A antagonist) and RS-102221 (5-HT2C antagonist) caused a notably and a mild reduction of the 5-HT-induced contractions, respectively, with no differences seen between sensitized and non-sensitized tissues. BW723C86 (5-HT2B agonist) did not induce contractile responses and RS-127445 (5-HT2B antagonist) did not modify the contractile responses to 5-HT. In non-sensitized aortas, the pattern of protein expression of receptors was 5HT2B>5-HT2A=5-HT2C, which did not change in sensitized animals. In conclusion, we found that allergic sensitization increased the aorta contractile responses to 5-HT, partly mediated by enhanced responses of 5-HT2A receptors, which was unrelated to changes in the expression of these receptors.

Fig. 1

Effect of sensitization and 5-HT₂ receptor family agonists and antagonists on contractile responses of guinea pig aortas. Inset in the upper right panel shows representative recordings of the 5-HT-induced contraction in sensitized (S) and non-sensitized (NS) aorta rings. (A) The response of sensitized (closed circles) and non-sensitized (open circles) aortas to 5-HT. (B–D) The responses to agonists of 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors (TCB-2, BW723C86, and WAY161503, respectively, all at a concentration of 100 μM). (E–G) The effect of antagonists of 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors (MDL 100907, RS-127445, and RS-102221, respectively, all at a concentration of 10 nM) added to the organ bath 20 min prior to 5-HT. (H–I) The already mentioned contractile responses measured as area under the curve. Symbols represent the mean ± standard error of n=8 experiments per group. * p<0.05 and ** p<0.01 after Student’s t-test (A-G) or ANOVA followed by Student’s t-test with Bonferroni correction (H, I).

Fig. 2

Protein expression of 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors in aortas isolated from non-sensitized and sensitized guinea pigs. There are no differences in the expression of 5-HT₂ receptor family in aortas measured by Western Blot analysis (ANOVA followed by Student’s t-test with Bonferroni correction). Data are expressed by mean ± standard error (n=5 for each group). NS=non-sensitized, S=sensitized.