Functional significance of PACAP receptors in regulating secretion and synthesis of vasopressi

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PACAP-containing axon terminals innervate arginine-vasopressin (AVP)-containing neurons in the rat hypothalamic supraoptic nucleus (SON). PACAP receptor (PACAPR) mRNA was expressed at high-levels in SON expressed in AVP-containing neurons. Although the pathway arising from PACAP/NA (noradrenalin)-containing neurons in the ventrolateral medulla is involved in the regulation of AVP, the precise mechanism of action and physiological significance of the coexistence of PACAP and NA still need to be investigated. Both PACAP and NA induced large increases in the [Ca2+]I in isolated AVP-containing neurons. When PACAP and NA were added together, they evoked larger increase in [Ca2+]I in AVP neurons. An inhibitor of PKA completely inhibited the PACAP-induced increase in [Ca2+]I, and partly the NA-induced increase in AVP-containing neurons. We found that T-type calcium channels might contribute to Ca2+ influx during action potentials through cAMP-PKA signaling pathway and L-type currents might contribute to the generation of bursting activity. PACAP and NA, co-released from the same axon terminals, may act synergistically to stimulate calcium signaling in AVP neurons, which is mediated by both cAMP-PKA pathway and L-type Ca2+ channel. PACAP/NA may regulate the functions of AVP-containing neurons which participate in the control of plasma osmolarity and blood pressure.