Dermal receptors

Dermal Receptors and Depth Sensitivity. Experimentally, dermal sensations can be accurately localized. They are the mechanoreceptors, thermoreceptors, and nociceptors. They transmit a wide variety of sensations like pressure, distension, contact, vibration, itch, tickling, cold, and pain. All of the above-mentioned sensations are allocated to the psycho-algesic area in the posterior central gyrus of the cerebral cortex. These stimuli can be localized with different degrees of resolution. The degree of accuracy with which two locally adjacent stimuli can be distinguished is shown by the following parameters ... 

Fitzhugh DJ, Naik S, Gonzalez E, Caughman SW, Hwang ST. CC chemokine receptor 6 (CCR6) is a marker for memory T cells that arrest on activated human dermal micro vascular endothelium under shear stress. J Invest Dermatol 2000 115(2) 332. 

With respect to vasodilation, niacin-elicited vasodilation requires the activation of GPR109A in skin Langerhans cells [34,35], which then triggers the release of arachidonic acid from membrane phospholipids and its subsequent metabolism to PGD2. The production of PGD2 then activates DPI receptors in dermal blood vessels to cause vasodilation [36]. 

Given the overwhelming influence of the physical properties of skin in determining bioavailabilities via the dermal route, assessment of dermal penetration is one area in metabolism and toxicology where in vitro methods can be effectively used to predict in vivo results and to screen chemicals. Apparatus and equipment exist that one can use to maintain sections of skin (obtained from euthanized animals or from human cadavers or surgical discard) for such experiments (Holland et al., 1984). These apparatus are set up to maintain the metabolic integrity of the skin sample between two reservoirs the one on the stratum comeum side, called the application reservoir and the one on the subcutaneous side, called the receptor reservoir. One simply places radiolabeled test material in the application reservoir and collects samples from the receptor fluid at various time points. 

Ohtani T, Aiba S, Mizuashi M, Mollah ZU, Nakagawa S, Tagami H H, and H2 histamine receptors are absent on Langerhans cells and present on dermal dendritic cells. J Invest Dermatol 2003 121 1073-1079. 

EMLA applied to intact skin provides dermal analgesia by the release of lidocaine and prilocaine from the cream into the epidermal and dermal layers of the skin. There is cumulation of lidocaine and prilocaine in the vicinity of dermal pain receptors and nerve endings. The quality and duration of dermal analgesia depends primarily on the duration of application. EMLA should be applied 1-2 hours before the planned intervention, e.g. venepuncture, split skin harvesting. 

Polybrominated Diphenyl Ethers. No information was located regarding dermal absorption of PBDEs in humans. The only information regarding dermal absorption in animals is that from a study of absorption in an in vitro preparation (Hughes et al. 2001). In that study, " C-dccaBDE dissolved in tetrahydrofuran was applied to dorsal skin (three dose levels) excised from adult hairless female mice and fractions of receptor fluid were collected over a 24-hour period. Transfer of radioactivity to the receptor fluid was minimal, only 0.07 to 0.34% of the applied radioactivity. Two to 20% of the radioactivity was found in the skin, and the lowest dose applied had the highest percentage of the dose in the skin. Washing the skin with solvent 24 hours after application removed 77-92% of the applied dose. In this study, decaDBE did not easily penetrate the skin, but inferences to dermal absorption in humans based on these limited results may not be appropriate. 

Immunoreactivity towards the frog dermal peptide [D-Ala2]deltorphin I, a selective ligand for delta opioid receptors, is reportedly present in high abundance in goblet cells of the rat jejunal mucosa, from which it may be secreted into the intestinal lumen [40]. Peptide-positive epithelial cells can be detected in the late fetal period [41]. Deltorphinlike immunoreactivity is not detectable in the enteric nervous system, and its precise chemical identity and functional significance remain to be determined. 

FcyRIIa (CD32a) is expressed in small-vessel endothelium in the papillary (superficial and periadnexal) dermis [27], Binding of IgG or immune complexes to isolated human dermal microvessel endothelial cells initiates rapid receptor cross-linking, intracellular Ca fluxes, and endosomal internalization of the IgG-FCyRIIa complexes [27], FcRn is expressed principally in basal and suprabasal human keratinocytes in normal epidermis [176] and is also expressed in mouse skin [62], In healthy adult human volunteers, dermal interstitial fluid endogenous IgG levels were demonstrated to be 30% of plasma IgG levels [59]. 

The results of the studies conducted on the 14 chemicals selected by the ILSI project were summarised by Eastin et al. (2001). Most studies confirmed the hypothesis that the dermal Tg.AC model responds to both mutagenic and nonmutagenic carcinogens. However, data from these studies suggested that the mechanism of action could be fundamental in obtaining the expected positive response. For example, topical application of ethinyl oestradiol, clofibrate and diethylstilbestrol gave clear positive results, whereas cyclosporin A was positive only in females and melphalan, phenacetin and cyclophosphamide did not produce any papillomas at SOA. The lack of receptor sites in the skin for these last compounds or selectivity between tissues for proliferative activity of some chemicals, could explain the negative responses. 

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