Modifications of plasma 5-HT concentrations during the allergic bronchoconstriction in guinea pigs

Abstract

Several contractile mediators involved in the antigen-induced airway obstruction have been identified, but the role of 5-HT (5-hydroxytryptamine or serotonin) has been scantily investigated. In this work, the potential role of 5-HT in the allergic bronchoconstriction was evaluated through a pharmacological approach and plasma 5-HT measurement in blood samples from the right and left ventricles of anesthetized guinea-pigs. Intravenous 5-HT caused a dose-dependent increase of the lung resistance in anesthetized, nonsensitized guinea pigs. Likewise, in sensitized animals the antigenic challenge with ovalbumin also caused a transient bronchoconstriction (356 ± 60% the basal value), which was largely inhibited by the blockade of serotonergic receptors with methiothepin plus tropisetron (134 ± 10%, P = .007). Sensitized animals tended to have plasma 5-HT concentrations higher than nonsensitized controls, and shortly after the peak of the allergic bronchoconstriction the 5-HT levels in the left ventricle (blood flowing out from lungs) tended to be higher than in the right ventricle (blood entering the lungs), although data dispersion precluded the obtaining of statistical significance. Interestingly, the degree of bronchoconstriction highly correlated with the concentrations of 5-HT found in the left ventricle and measured either in platelet-rich plasma (r = 0.97 P = .007) or platelet-poor plasma (r = 0.97, P = .006). After the obstructive response subsided these correlations were lost, but now the degree of bronchoconstriction turned to be correlated with 5-HT concentration in platelet concentrate (r = 0.76, P = .03). In conclusion, our results suggested that 5-HT is actively released from lungs during the antigenic challenge and that this autacoid is involved in the generation of the airway obstruction.

Allergic Sensitization Increases Contractile Responses to 5-HT in Guinea Pig Aorta

“…Thus, clinical studies have demonstrated that plasma levels of 5-HT were elevated in a variety of CVD-related pathologies, including hypertension, coronary artery disease, valvular heart disease, atherothrombosis, atherosclerosis, and myocardial infarction (Kaumann and Levy 2006). Likewise, increased 5-HT blood levels were found in patients with asthma (Lechin et al 1996), as well as in animal models of asthma (Segura et al 2010, Arreola-Ramirez et al 2013. Moreover, platelets constitute the major source of 5-HT in blood, and it is known that, in humans, these elements are involved in disorders of the cardiovascular system (Papapanagiotou et al 2016), as well as in asthma (Idzko et al 2015).| Fig.…”

ADAM19 and HTR4 Variants and Pulmonary Function

“…11 While serotonin (5-HT) is best studied as neurotransmitter, 5-HT signaling plays an important role in many organ systems. 28 In the lung it is involved in control of breathing 28 and smooth muscle contractility 29 . Serotonin signaling including HTR4 is involved in human airway inflammation.…”

Neuroimmune Pathophysiology in Asthma

“…In addition, NT increases the migration of pulmonary DCs to draining lymph nodes and induces the expression of a Th2 profile in these cells (Müller et al, 2009). Additionally, ASM cells express 5-HT 2A/3/4/7 (Fernandez-Rodriguez et al, 2010;Segura et al, 2010) in MMAA, which mediates bronchoconstriction (Arreola-Ramírez et al, 2013), activating its receptors on parasympathetic ACh-containing neurons, resulting in the release of ACh (Figure 4; Fernandez-Rodriguez et al, 2010). Interestingly, TNF-α up-regulates the contraction mediated by 5-HT via the 5-HT 2A receptor (Adner et al, 2002).…”