Fig. 3From: Shared and independent roles of CGRP and PACAP in migraine pathophysiologySchematic of CGRP and PACAP signaling pathways. CGRP and PACAP can act via multiple receptors, as indicated. For simplicity, signaling pathways from generic receptors in a generic cell type are illustrated. In general, activation of both CGRP and PACAP receptors increase cAMP levels, which leads to protein kinase A (PKA) activation and EPAC1/2 activation. EPAC1/2 activation by PACAP is well-established, although activation by CGRP is less clear (dotted line). Canonical CGRP receptor, but not AMY1 CGRP receptor, and the PACAP receptor PAC1 can generate endosomal signals following β-arrestin-mediated receptor internalization. Activation of additional G protein pathways that elevate IP3 and calcium have been reported for PACAP and to a lesser extent CGRP (dotted lines). These pathways activate multiple downstream targets, including MAP kinases (MAPKs), ion channels, and genes, depending on the cell type. Created with BioRender.comBack to article page