Functional Significance of Colocalization of PACAP and Catecholamine in Nerve Terminals

• Published in: Annals of the New York Academy of Sciences 2000-01, Vol.921 (1), p.211-217
• Main Authors: SHIODA, SEIJI, YADA, TOSHIHIKO, MUROYA, SHINJI, URAMURA, SHIGEAKI, NAKAJO, SHIGEO, OHTAKI, HIROKAZU, HORI, TOSHIKO, SHIMODA, YOSHIMI, FUNAHASHI, HISAYUKI
• Format: Article
• Language: English
• Subjects: Animals; Arginine Vasopressin - metabolism; Calcium Signaling; Immunohistochemistry; Male; Nerve Endings - metabolism; Neuropeptides - metabolism; Norepinephrine - metabolism; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; Supraoptic Nucleus - metabolism
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2000.tb06968.x

: Medullary neurons containing pituitary adenylate cyclase‐activating polypeptide (PACAP) and noradrenalin (NA) project to the hypothalamus and they are involved in the regulation of arginine vasopressin (AVP) neurons. At the ultrastructural level, PACAP immunoreactivity was detected in the granular vesicles in catecholaminergic nerve terminals that made synaptic contact with AVP neurons. Both PACAP (at least 1 nM) and NA (at least 1 μmM) induced large increases in the cytosolic Ca2+ concentration ([Ca2+]i) in isolated AVP cells. PACAP at 0.1 nM and NA at 0.1 μmM had little effects, if any, on [Ca2+]i. However, when 0.1 nM PACAP and 0.1 μM NA were combined, they evoked large increase in [Ca2+]i in AVP neurons. An inhibitor of protein kinase A (PKA) completely inhibited the PACAP‐induced increase in [Ca2+]i, but only partly inhibited the NA‐induced increase in [Ca2+]i. In AVP cells that were prelabeled with quinacrine, PACAP and NA acted synergistically to induce a loss of quinacrine fluorescence, indicating secretion of neurosecretory granules in AVP neurons. The results suggest that PACAP and NA, coreleased from the same nerve terminals, act in synergy to evoke calcium signaling and secretion in AVP neurons, and that the synergism is mediated by the interaction between cAMP‐PKA pathway an as yet unidentified factor “X” linked to L‐type Ca2+ channels. The synergism between PACAP and NA may contribute to the regulation of AVP secretion under physiological conditions.