anandamide and cinnamaldehyde

Nasal transient receptor potential vanilloid 1 (TRPV1) stimulation with capsaicin produces serous and mucinous secretion in the human nasal airway. The primary aim of this study was to examine topical effects of various TRP ion channel agonists on symptoms and secretion of specific mucins: mucin 5 subtype AC (MUC5AC) and B (MUC5B).. Healthy individuals were subjected to nasal challenges with TRPV1 agonists (capsaicin, olvanil and anandamide), TRP ankyrin 1 (TRPA1) agonists (cinnamaldehyde and mustard oil) and a TRP melastatin 8 (TRPM8) agonist (menthol). Symptoms were monitored, and nasal lavages were analysed for MUC5AC and MUC5B, i.e. specific mucins associated with airway diseases. In separate groups of healthy subjects, nasal biopsies and brush samples were analysed for TRPV1 and MUC5B, using immunohistochemistry and RT-qPCR. Finally, calcium responses and ciliary beat frequency were measured on isolated ciliated epithelial cells.. All TRP agonists induced nasal pain or smart. Capsaicin, olvanil and mustard oil also produced rhinorrhea. Lavage fluids obtained after challenge with capsaicin and mustard oil indicated increased levels of MUC5B, whereas MUC5AC was unaffected. MUC5B and TRPV1 immunoreactivities were primarily localized to submucosal glands and peptidergic nerve fibres, respectively. Although trpv1 transcripts were detected in nasal brush samples, functional responses to capsaicin could not be induced in isolated ciliated epithelial cells.. Agonists of TRPV1 and TRPA1 induced MUC5B release in the human nasal airways in vivo. These findings may be of relevance with regard to the regulation of mucin production under physiological and pathophysiological conditions.

Topics: Acrolein; Administration, Intranasal; Adult; Aged; Arachidonic Acids; Biopsy; Calcium; Calcium Channels; Capsaicin; Cilia; Cross-Over Studies; Double-Blind Method; Endocannabinoids; Humans; Immunohistochemistry; Methanol; Middle Aged; Movement; Mucin 5AC; Mucin-5B; Mustard Plant; Nasal Lavage; Nasal Mucosa; Nerve Tissue Proteins; Pain; Pain Measurement; Plant Oils; Polyunsaturated Alkamides; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Sensory System Agents; Sweden; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPM Cation Channels; TRPV Cation Channels; Young Adult

Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1).. To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure.. Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms were monitored after each challenge and compared with symptoms reported following corresponding sham challenges. Symptoms recorded after challenge prior to pollen season were also compared with challenge-induced symptoms during pollen season.. The TRPV1, TRPA1 and TRPM8-activators produced sensory symptoms dominated by pain and smart. During seasonal allergen exposure, but not prior to season, TRPV1-activators also induced itch. Furthermore, the seasonal challenge to the TRPV1-activator olvanil was associated with rhinorrhoea.. Patients with allergic rhinitis feature an increased itch response to TRPV1 stimulation at seasonal allergen exposure. We suggest that this reflects part of the hyperresponsiveness that characterizes on-going allergic rhinitis. Intervention with the TRPV1-signalling pathway may offer potential treatments of this condition.

Topics: Acrolein; Adult; Allergens; Anti-Inflammatory Agents, Non-Steroidal; Antipruritics; Arachidonic Acids; Calcium Channel Blockers; Calcium Channels; Capsaicin; Endocannabinoids; Humans; Menthol; Mustard Plant; Nasal Provocation Tests; Nerve Tissue Proteins; Plant Oils; Polyunsaturated Alkamides; Pruritus; Rhinitis, Allergic, Seasonal; Sensory System Agents; Severity of Illness Index; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPM Cation Channels; TRPV Cation Channels