Asthmatic allergen inhalation sensitises carotid bodies to lysophosphatidic acid

Abstract

The carotid bodies are multimodal sensors that regulate various autonomic reflexes. Recent evidence demonstrates their role in immune reflex regulation. Our previous studies using the allergen (ovalbumin) sensitised and exposed Brown Norway rat model of asthma suggest that carotid bodies mediate asthmatic bronchoconstriction through a lysophosphatidic acid (LPA) receptor (LPAr)-protein kinase C epsilon (PKCε)-transient receptor potential vanilloid one channel (TRPV1) pathway. Whilst naïve carotid bodies respond to LPA, whether their response to LPA is enhanced in asthma is unknown. Here, we show that asthmatic sensitisation of Brown Norway rats involving repeated aerosolised allergen challenges over 6 days, results in an augmentation of the carotid bodies’ acute sensitivity to LPA. Increased expression of LPAr in the carotid bodies and petrosal ganglia likely contributed to this sensitivity. Importantly, allergen sensitisation of the carotid bodies to LPA did not alter their hypoxic response, nor did hypoxia augment LPA sensitivity acutely. Our data demonstrate the ability of allergens to sensitise the carotid bodies, highlighting the likely role of the carotid bodies and blood-borne inflammatory mediators in asthma.

TRPM7 channels regulate breathing during sleep in obesity by acting peripherally in the carotid bodies

“…Similar results have been reported with other transient receptor potential channels expressed in the CB. Transient receptor potential vanilloid one (TRPV1) sensitizes the CB independently of the hypoxic sensitivity possibly through a post‐synaptic pathway in asthmatic rats (Jendzjowsky, Roy, & Wilson et al., 2021; Jendzjowsky, Roy, Iftinca et al., 2021). TRPM7 could also regulate CB activity through alternative molecular pathways.…”

Commonalities and differences in carotid body dysfunction in hypertension and heart failure

“…In addition, exogenous LPA infusion raised the blood pressure of rodents (Tokumura et al, 1978). Interestingly, increased plasma LPA was demonstrated to activate carotid bodies via both LPA receptors (LPAr) and transient receptor potential vanilloid one (TRPV1) (Jendzjowsky et al, 2018(Jendzjowsky et al, , 2021a(Jendzjowsky et al, , 2021b. Therefore, it would not be surprising if LPA was also involved with carotid body sensitisation during the development of atherosclerotic plaque in patients that are or will be hypertensive or develop HF in early stages.…”

Pathogen recognition by sensory neurons: hypotheses on the specificity of sensory neuron signaling

“…In this regard, an additional line of defense would be recruited if pathogenic infiltration should enter the blood stream; the carotid chemoreceptors ( 16 ) the main sensory organ which patrols hemolytic homeostasis ( 15 ) would also be stimulated. Evidence demonstrates the carotid chemoreceptors’ ability to detect pathogenic patterns ( 16 ) as well as substances released in response to disease states/allergy ( 110 , 111 ) as their composition of pathogenic detection is notable ( 38 ). We have demonstrated the possibility for this biologic scenario to occur in our dual vagus and carotid chemoreceptor preparation ( 43 ).…”