PACAP, VIP, and PHI: effects on AC-, PLC-, and PLD-driven signaling systems in the primary glial cell cultures.
Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and peptide histidine-isoleucine (PHI) are members of a superfamily of structurally related peptides widely distributed in the body and displaying pleiotropic biological activities. All these peptides are known to act via common receptors-VPAC1 and VPAC2. In addition, the effects of PACAP are mediated through its specific receptor named PAC1. The main signal transduction pathway of the mentioned receptors is adenylyl cyclase (AC)-->cAMP system. PACAP and VIP may also signal through receptor-linked phospholipase C (PLC)-->IP3/DAG-->PKC and phospholipase D (PLD)-->phosphatidic acid (PA) pathways. In the present article, we have studied the effects of PACAP, VIP, and PHI (0.001-5000 nM) on the AC-, PLC-, and PLD-driven signaling pathways in rat primary glial cell (astrocytes) cultures. All tested peptides dose-dependently and strongly stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in this experimental model, displaying the following rank order of potency: PACAP >> VIP > or = PHI. Their effects on PLC-IP3/DAG were weaker, while only PACAP and VIP (0.1-5 microM) significantly stimulated PLD activity. The obtained results showed that rat cerebral cortex-derived astrocytes are responsive to PACAP, VIP and PHI/PHM and possess PAC1 and likely VPAC-type receptors linked to activation of AC-cAMP-, PLC-IP3/DAG-, and PLD-PA signaling systems.
Dejda
Agnieszka
A
Centre for Medical Biology, Polish Academy of Sciences, 106 Lodowa Street, 93-232 Lodz, Poland. adejda@cbm.pan.pl
Jozwiak-Bebenista
Marta
M
Nowak
Jerzy Z
JZ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D018929:Cell Culture Techniques; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology*; D010446:Peptide Fragments / Q000494:pharmacology; D010451:Peptide PHI / Q000494:pharmacology*; D010739:Phospholipase D / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D010738:Type C Phospholipases / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D010446:Peptide Fragments; D010451:Peptide PHI; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D010740:Phospholipases; D010738:Type C Phospholipases; D010739:Phospholipase D; D000262:Adenylyl Cyclases