title: Functional activity of serotoninergic and melatoninergic systems expressed in the skin.
abstract: We tested the expression of genes coding receptors of a cutaneous serotoninergic/melatoninergic system in whole human skin and in normal and pathologic cultured skin cells. Evaluation of serotonin (5HT), melatonin (MT), and melatonin-related receptors (MRR) showed expression of the isoforms 5HT2B, 5HT7, and MT1 genes in almost all the tested samples. Expression of other isoforms was less prevalent; 5HT2C, MRR, and MT2 were rarely detected. We also found novel isoforms for MT2, MRR, and 5HT2B and documented the process of RNA editing for 5HT2C. Testing for functional activity of these receptors with serotonin and melatonin (10(-14) to 10(-10) M) showed variable effects depending on cell type and culture conditions. Thus, serotonin stimulated proliferation of melanocytes in medium deprived of growth factors, while inhibiting cell growth in the presence of growth factors. Melatonin inhibited both apoptosis of HaCaT keratinocytes incubated in serum-free media, and proliferation of cells cultured in medium supplemented with serum. Melatonin also increased the numbers of viable fibroblasts incubated in serum free medium. N-acetylserotonin (NAS) and 5 methoxytryptamine (5MTT) were generally without effect on cell proliferation, with the exception of an inhibition of melanocyte proliferation at the higher 5MTT concentration of 10(-10) M. Thus, skin cells represent a true target for the products of the serotoninergic/melatoninergic cutaneous pathway with their actions modulating cell proliferation or viability.
authors.affiliation: Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. aslominski@utmem.edu
authors.forename: Andrzej
authors.initials: A
authors.lastname: Slominski
authors.forename: Alexander
authors.initials: A
authors.lastname: Pisarchik
authors.forename: Blazej
authors.initials: B
authors.lastname: Zbytek
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
authors.forename: Söbia
authors.initials: S
authors.lastname: Kauser
authors.forename: Jacobo
authors.initials: J
authors.lastname: Wortsman
mesh_terms: D008735:5-Methoxytryptamine / Q000494:pharmacology; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008550:Melatonin / Q000494:pharmacology; D010641:Phenotype; D010902:Pituitary Gland / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D044094:Receptors, Melatonin; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D011985:Receptors, Serotonin; D012701:Serotonin; D008735:5-Methoxytryptamine; D008550:Melatonin; C006389:N-acetylserotonin