PACAP attenuates 5-HT, histamine, and ATP-evoked Ca2+ transients in astrocytes.

Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective properties and plays an important role in neuroinflammation. PACAP38 interacts with its receptors, PAC1, and VPAC, on astrocytes at 10(-8) M to induce biphasic Ca2+ transients, which were reduced to a single transient by the PAC1-blocking PACAP antagonist PACAP6-38. At 10(-12) M even the single transient, corresponding to PAC1 was blocked. PACAP-induced Ca2+ transients were more pronounced in astrocytes cocultured with brain endothelial cells than in monocultured astrocytes, indicating that astrocytes that receive signals from microvessels develop more sensitive signal transduction systems for Ca. In this sensitive system, PACAP38 attenuated 5-HT, histamine, and ATP-evoked Ca2+ transients, showing the anti-inflammatory properties of PACAP.