D-Aspartate affects secretory activity in rat Harderian gland: molecular mechanism and functional significance.
In this paper, the role of D-aspartate in the rat Harderian gland (HG) was investigated by histochemical, ultrastructural, and biochemical analyses. In this gland, substantial amounts of endogenous D-Asp were detected, along with aspartate racemases that convert D-Asp to L-Asp and vice versa. We found that the gland was capable of uptaking and accumulating exogenously administered D-Asp. D-Asp acute treatment markedly increased lipid and porphyrin secretion and induced a powerful hyperaemia in inter-acinar interstitial tissue. Since D-Asp is known to be recognized by NMDA receptors, the expression of such receptors in rat HG led us to the hypothesis that D-Asp acute treatment induced the activation of the extracellular signal-regulated protein kinase (ERK) and nitric oxide synthase (NOS) pathways mediated by NMDA. Interestingly, as a result of enhanced oxidative stress due to increased porphyrin secretion, the revealed activation of the stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) pro-apoptotic pathway was probably triggered by the gland itself to preserve its cellular integrity.
Monteforte
Rossella
R
Dipartimento di Scienze della Vita, Seconda Università degli Studi di Napoli, via Vivaldi, 43-81100, Caserta, Italy.
Santillo
Alessandra
A
Di Giovanni
Marcello
M
D'Aniello
Antimo
A
Di Maro
Antimo
A
Chieffi Baccari
Gabriella
G
D000591:Amino Acid Isomerases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D000242:Cyclic AMP / Q000819:agonists / Q000378:metabolism; D006152:Cyclic GMP / Q000819:agonists / Q000378:metabolism; D026603:D-Aspartic Acid / Q000008:administration & dosage / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006243:Harderian Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000187:drug effects / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D011166:Porphyrins / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D011166:Porphyrins; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D026603:D-Aspartic Acid; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D000591:Amino Acid Isomerases; D006152:Cyclic GMP