D-aspartate modulates transcriptional activity in Harderian gland of frog, Rana esculenta: Morphological and molecular evidence

In the green frog, Rana esculenta, a substantial amount Of D-aspartate (D-Asp) is found enclogenously 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 mu mol/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. Atatirnewhenthe 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. (c) 2005 Wiley-Liss, Inc.