Calcium signal-mediated expression of the vasoactive intestinal polypeptide gene and its small contribution to activity-dependent survival of mouse cerebellar granule cells.
We have demonstrated previously in primary cultures of mouse cerebellar granule cells (CGCs) that endogenously synthesized pituitary adenylate cyclase-activating polypeptide (PACAP) contributes at least in part to the activity-dependent survival of CGCs (Tabuchi et al. [2001] Neurosci. Res. 39:85-93). In this study, we have demonstrated that expression of vasoactive intestinal polypeptide (VIP), a member of the same VIP/secretin/glucagon family as PACAP, was activated markedly by Ca(2+) influx through L-type voltage-dependent Ca(2+) channels (L-VDCCs), which could be induced under the depolarizing condition induced by high concentration of potassium (K(+)) in the medium. The activation of VIP mRNA expression, different from that of PACAP, was dependent partly on de novo protein synthesis. On the other hand, mRNA expression of secretin and PACAP/VIP receptors (PAC(1), VPAC(1), and VPAC(2)) was not activated by the Ca(2+) influx; rather, PAC(1) mRNA expression was reduced. Exogenously added VIP prevented apoptosis of CGCs under nondepolarizing conditions, the effect of which was mediated specifically through the VPAC(1) receptor. Furthermore, the survival of CGCs under depolarizing conditions could be mediated partly through VPAC(1), the contribution of which was much less than that of PAC(1). These findings indicate that PACAP and VIP genes are coordinately activated by the Ca(2+) signals in CGCs, but the contribution of VIP to the activity-dependent survival of CGCs is quite small.
Fukuchi
Mamoru
M
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Sakuragawa
Saori
S
Tabuchi
Akiko
A
Tsuda
Masaaki
M
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C029937:secretin receptor; D014660:Vasoactive Intestinal Peptide; D011188:Potassium