Multiple signal pathways coupling VIP and PACAP receptors to calcium channels in hamster submandibular ganglion neurons

Abstract

The Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two novel neuropeptides which produce particular biological effects caused by interaction with G-protein-coupled receptors. We have shown in a previous study where VIP and PACAP 38 inhibit voltage-dependent calcium channel (VDCC) currents (I Ca) via G-proteins in hamster submandibular ganglion (SMG) neurons. In this study, we attempt to further characterize the signal transduction pathways of VIP-and PACAP 38-induced modulation of I Ca. Application of 1 μM VIP and PACAP 38 inhibited I Ca by 33.0±3.1% and 36.8±2.6%, respectively (mean±S.E.M., n=8). Application of strong voltage prepulse attenuated PACAP 38-induced inhibition of I Ca. Pretreatment of cAMP dependent protein kinase (PKA) activator attenuated VIP-induced inhibition, but not the PACAP 38-induced inhibition. Intracellular dialysis of the PKA inhibitor attenuated the VIP-induced inhibition, but not the PACAP 38-induced inhibition. Pretreatment of protein kinase C (PKC) activator and inhibitor attenuated VIP-induced inhibition, but not the PACAP 38-induced inhibition. Pretreatment of cholera toxin (CTX) attenuated PACAP 38-induced inhibition of I Ca. These findings indicate that there are multiple signaling pathways in VIP and PACAP 38-induced inhibitions of I Ca: one pathway would be the VPAC 1/VPAC 2 receptors-induced inhibition involving both the PKA and PKC, and another one concerns the PAC 1 receptor-induced inhibition via G s-protein βγ subunits. The VIP-and PACAP 38-induced facilitation of I Ca can be observed in the SMG neurons in addition to inhibiting of I Ca.