title: VIP and the potent analog, stearyl-Nle(17)-VIP, induce proliferation of keratinocytes.
abstract: Vasoactive intestinal polypeptide (VIP) exhibits effects on cell proliferation. Here, VIP, as well as the related peptide, pituitary adenylate cyclase activating peptide (PACAP), promoted human keratinocyte division. Stearyl-Nle(17)-VIP (SNV) was identified as a superior mitogen for the keratinocytic cell line, HaCaT, both in potency (fM-nM concentrations) and efficacy. Reverse transcription-polymerase chain reaction detected in keratinocytes only PACAP mRNA and the relevant type 1 (VPAC(1)R) and type 2 (VPAC(2)R) receptors, while VIP and the third receptor (PAC(1)) transcripts were absent. Upon serum deprivation of HaCaT, the VPAC(1)R mRNA was apparently increased, while the VPAC(2)R transcript remained constant. Incubation of HaCaT with VIP or SNV increased nitric oxide and cGMP formation. In contrast to VIP, SNV did not augment cAMP. Thus, the paracrine VIP, and autocrine PACAP, related pathways leading to keratinocyte proliferation may involve VPAC(1)R/VPAC(2)R and nitric oxide/cGMP production.
authors.affiliation: Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Granoth
authors.forename: M
authors.initials: M
authors.lastname: Fridkin
authors.forename: I
authors.initials: I
authors.lastname: Gozes
mesh_terms: D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000473:pathology; D009479:Neuropeptides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010455:Peptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C495401:ADCYAP1 protein, human; D016895:Culture Media, Serum-Free; D009479:Neuropeptides; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D014665:Vasodilator Agents; C086770:stearyl-norleucine(17)-vasoactive intestinal peptide; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D006152:Cyclic GMP