title: D-aspartate modulates transcriptional activity in Harderian gland of frog, Rana esculenta: Morphological and molecular evidence.
abstract: In the green frog, Rana esculenta, a substantial amount of D-aspartate (D-Asp) is found endogenously within the Harderian gland (HG) following its synthesis from L-aspartate (L-Asp) by an aspartate racemase. The frog HG is an orbital seromucoid gland that displays seasonal changes in secretory activity. Our in vivo experiments, consisting of i.p. injection of 2.0 mumol/g b.w. D-Asp in frogs collected during two periods of differing glandular activity (high or medium-low secretory activity), revealed that HG can to take up and accumulate D-Asp and that this amino acid may modulate the exocrine secretion through a kinase pathway. At a time when the gland shows relatively low secretory activity, i.p. administration of D-Asp rapidly induced activation of ERK1 and an increase in cells active in RNA synthesis. This increase in transcriptional activity was followed by a significant increase in mucous secretion. By contrast, administration of exogenous D-Asp when HG was showing high activity rapidly induced inhibition of both ERK1 and transcriptional activity. Since D-Asp is known to be recognized by receptors for N-methyl-D-aspartic acid (NMDA), it is possible that in the HG, D-Asp mediated NMDA activation may enhance the kinase pathway. The above activation of opposing stimulatory and inhibitory processes could reflect different levels of NMDA-receptor activity, which could vary as a function of the level of gland activity. This study provides the first evidence of a role for this excitatory amino acid in exocrine secretion. The effects of D-Asp in HG appear to be specific since they were not seen in frogs treated with other D- or L-amino acids with known excitatory effects on neurosecretion.
authors.affiliation: Dip. Scienze della Vita, Seconda Università di Napoli, via Vivaldi, Caserta, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Raucci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Santillo
authors.forename: Antimo
authors.initials: A
authors.lastname: D'Aniello
authors.forename: Paolo
authors.initials: P
authors.lastname: Chieffi
authors.forename: Gabriella Chieffi
authors.initials: GC
authors.lastname: Baccari
mesh_terms: D000818:Animals; D026603:D-Aspartic Acid / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006243:Harderian Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006651:Histocytochemistry; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019998:Racemases and Epimerases / Q000378:metabolism; D011893:Rana esculenta; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D026603:D-Aspartic Acid; D048052:Mitogen-Activated Protein Kinase 3; D019998:Racemases and Epimerases