TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis.

Allergic contact dermatitis is a common skin disease associated with inflammation and persistent pruritus. Transient receptor potential (TRP) ion channels in skin-innervating sensory neurons mediate acute inflammatory and pruritic responses following exogenous stimulation and may contribute to allergic responses. Genetic ablation or pharmacological inhibition of TRPA1, but not TRPV1, inhibited skin edema, keratinocyte hyperplasia, nerve growth, leukocyte infiltration, and antihistamine-resistant scratching behavior in mice exposed to the haptens, oxazolone and urushiol, the contact allergen of poison ivy. Hapten-challenged skin of TRPA1-deficient mice contained diminished levels of inflammatory cytokines, nerve growth factor, and endogenous pruritogens, such as substance P (SP) and serotonin. TRPA1-deficient sensory neurons were defective in SP signaling, and SP-induced scratching behavior was abolished in Trpa1(-/-) mice. SP receptor antagonists, such as aprepitant inhibited both hapten-induced cutaneous inflammation and scratching behavior. These findings support a central role for TRPA1 and SP in the integration of immune and neuronal mechanisms leading to chronic inflammatory responses and pruritus associated with contact dermatitis.

Preparation and Properties of Cnidocytes from the Sea Anemone Anthopleura elegantissima.

Cnidocytes were isolated from the tentacles and acrorhagi of Anthopleura elegantissima by enzymatic treatment with papain followed by centrifugation in a Percoll-containing medium to produce a concentrated fraction of these cells. The morphology of the isolated cells, as revealed by light and electron microscopy, showed that these cells had intact plasma membranes and was comparable to that of cells in situ. Comparison of the ability of different substances to induce discharge in isolated and in situ cnidocytes showed that the responsiveness of isolated cells was reduced, but not abolished, compared to in situ cnidocytes. Electrophysiological recordings made from cnidocytes isolated from acrorhagi showed that these cells possess voltage-activated ionic currents, further proof that the isolation procedure did not effect the integrity of the plasma membrane. Discharge did not occur with changes in membrane potential.