Symptoms of bronchospasm and chest tightness caused by widow spider bites have led to an international research group, including scientists from Sydney’s Woolcock Institute, describing a potential new target for asthma therapy.
Working with young Dutch researcher Dr Alen Faiz, they found latrophilin (LPHN) receptors are expressed more commonly in airway smooth muscle cells of patients with asthma compared to healthy controls.
A single nucleotide polymorphism in the LPHN 1 gene encoding the receptor was identified in the asthmatic patients, and findings in a mouse model supported the key role of the receptors.
“When activated, LHPNs regulated airway smooth muscle cell adhesion and proliferation in vitro, and promoted contraction of mouse airways,” they reported in Thorax.
“Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.”
Although many studies had explored the pathological changes in smooth muscle cells in asthmatic airways, including their increased proliferation, little had been known about the receptors and pathways that led to this hypercontractile state.
A potential role of LPHNs was suggested by research into the pharmacology of widow spiders – the Latrodectus genus. The receptors were able to bind to the toxin, and were best known for their role in the release of neurotransmitters, including acetylcholine, from sensory and motor neurones, and also for the release of insulin from endocrine cells.
This latest project used tissue from biopsies and explanted lungs from patients with asthma and healthy controls, then isolated and cultured airway smooth muscle cells in culture, allowing a series of sophisticated studies on receptor binding.
Spider venom and another ligand known to bind with the receptors were tested in mouse airways and confirmed to cause muscle contraction. The findings were consistent with the symptoms caused by widow spider bites, and supported the use of atropine to address the cholinergic effects as well as standard treatment with antivenom.
“The bottom line is that latrophilins may contribute to airway smooth muscle contraction as well as adhesion and proliferation and their increased expression in asthmatic smooth muscle cells may affect the asthma phenotype,” Dr Faiz and his colleagues concluded.