It is now more than 15 years since the molecular structures of the major prostanoid receptors were elucidated. Since then, substantial progress has been achieved with respect to distribution and function, signal transduction mechanisms, and the design of agonists and antagonists ( ). This review systematically details these advances. More recent developments in prostanoid receptor research are included. The DP2 receptor, also termed CRTH2, has little structural resemblance to DP1 and other receptors described in the original prostanoid receptor classification. DP2 receptors are more closely related to chemoattractant receptors. Prostanoid receptors have also been found to heterodimerize with other prostanoid receptor subtypes and nonprostanoids. This may extend signal transduction pathways and create new ligand recognition sites: prostacyclin/thromboxane A2 heterodimeric receptors for 8- epi -prostaglandin E2, wild-type/alternative (alt4) heterodimers for the prostaglandin FP receptor for bimatoprost and the prostamides. It is anticipated that the 15 years of research progress described herein will lead to novel therapeutic entities.

https://pharmrev.aspetjournals.org/content/pharmrev/63/3/471.full.pdf

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Itch, or pruritus, is the predominant symptom associated with acute and chronic cutaneous disease, and in some cases may be debilitating. To date, there is no single universally effective anti-itch treatment. Because the pathophysiology of itch in most cutaneous or systemic disorders remains unclear, antipruritic therapy is often directed against a variety of targets, including the epidermal barrier, immune system, or the nervous system. Topical therapy is the mainstay of dermatologic management of acute or localized itch or in patients with contraindications to systemic therapies. This review will summarize current topical therapies to treat pruritus and discuss potential future therapies.

Topical therapies for pruritus.

We investigated the effects of a single dose of mouse interleukin-31 (IL-31) on scratching behaviour in comparison with spontaneous skin-lesion- or serotonin (5-HT)- induced scratching behaviour in NC/Nga and BALB/c mice. Intradermal (i.d.) injection of IL-31 caused a gradual increase in long-lasting scratching (LLS, over 1.5 s) about 3 h after administration followed by a gradual decrease for over 24 h after administration. I.d. injection of IL-31 significantly increased the total LLS counts/24 h but not short-lasting scratching (SLS, 0.3-1.5 s). In skin-lesioned NC/Nga mice, the LLS but not SLS counts were significantly higher than those in non-skin-lesioned NC/Nga mice. We also investigated 5-HT-induced scratching in BALB/c mice, SLS but not LLS increased immediately after the injection and then decreased to baseline after at 20 min. These results suggest that IL-31 may participate in the sensation of itching and promote scratching behaviour in skin-lesioned NC/Nga mice, an animal model of atopic dermatitis (AD).

A single dose of interleukin‐31 (IL‐31) causes continuous itch‐associated scratching behaviour in mice

Research about the skin barrier and its properties has increased significantly since the 60s, with studies that indicated its resistance when isolated, as well as its particularities in relation to skin permeability. At the same time, description of Odland bodies helped to understand how stratum corneum stability is maintained. The âbrick and mortarâ model is the most accepted so far. In this analogy, the corneocytes are the bricks and the intercellular lipids are the mortar. Currently, there is concrete evidence that the stratum corneum is an active metabolic structure that holds adaptive functions, interacting dynamically with the underlying epidermal layers. The skin barrier also plays a role in the inflammatory response through melanocyte activation, angiogenesis, and fibroplasia. The intensity of this response will essentially depend on the severity of the injury. Skin barrier abnormalities in atopic dermatitis are clinically observed by the presence of dry skin, a common and significant symptom which constitutes a diagnostic and monitoring parameter. The stratum corneum hydration level and transepidermal water loss are associated with the level of damage to the barrier, representing biophysical parameters. These parameters help doctors monitor patients in a less invasive and more sensitive manner.

http://www.scielo.br/pdf/abd/v85n2/en_09.pdf

Barreira cutânea na dermatite atópica

The Return of the Mast Cell: New Roles in Neuroimmune Itch Biology.

Effects of TS-022, a newly developed prostanoid DP1 receptor agonist, on experimental pruritus, cutaneous barrier disruptions and atopic dermatitis in mice

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Effects of TS-022, a newly developed prostanoid DP1 receptor agonist, on experimental pruritus, cutaneous barrier disruptions and atopic dermatitis in mice