Pituitary adenylate cyclase-activating polypeptide (PACAP): a novel regulator of vasopressin-containing neurons

Pituitary adenylate cyclase-activating polypeptide (PACAP) was localized in nerve terminals that innervate arginine-vasopressin (AVP)-containing neurons in the rat hypothalamic supraoptic nucleus (SON). PACAP receptor (PACAPR) mRNA was expressed at high-levels in AVP-containing neurons in the SON, but at very low-levels in oxytocin-containing neurons. PACAPR-like immunoreactivity was found in SON and it was observed in the post-synaptic membranes as well as on the rough endoplasmic reticulum and cytoplasmic matrices in the magnocellular neurons. Doses of PACAP in the nanomolar range increased cytoplasmic Ca²⁺ concentrations ([Ca²⁺]_i) in AVP-containing neurons; the increase in [Ca²⁺]_i was inhibited by a protein kinase A blocker. These findings suggest that PACAP serves as a transmitter and/or modulator and the activation of PACAPR stimulates a cAMP-protein kinase A pathway which in turn evokes the Ca²⁺ signaling system. It is hypothesized that PACAP regulates the functions of AVP-containing neurons which participate in the control of plasma osmolarity and blood pressure.