PACAP and its receptors exert pleiotropic effects in the nervous system by activating multiple signaling pathways

Chengji Zhou, Seiji Shioda, Toshihiko Yada, Nobuya Inagaki, Samuel J. Pleasure, Sakae Kikuyama

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally isolated from the ovine brain in 1989 as a novel hypothalamic hormone that potently activates adenylate cyclase to produce cyclic AMP in pituitary cells. This neuropeptide belongs to the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily, and exists in two amidated forms as PACAP38 (38-amino acid residues) and PACAP27 derived from the same precursor. The primary structure of PACAP has been remarkably conserved throughout evolution among tunicata, ichthyopsida, amphibia and mammalia, and a PACAP-like neuropeptide has also been determined in Drosophila. Both PACAP and its receptors are mainly distributed in the nervous and endocrine systems showing pleiotropic functions with high potency. There are three types of receptors with high PACAP-binding affinity and with different tissue-distribution patterns. All of them belong to G-protein-coupled receptor superfamily with seven transmembrane domains. PAC1 is the PACAP-specific receptor and exists in at least eight splice variants which couple to different intracellular signal transduction pathways. VPAC1 and VPAC2 are the common receptors for both PACAP and VIP, which are coupled to adenylate cyclase. This review article presents and discusses an update on PACAP research and its pleiotropic physiological functions based on multiple receptor-mediated signaling mechanisms in both the central and peripheral nervous system, including the regulation of hypothalamic neurosecretion, homeostatic control of circadian clock and behavioral actions, involvement in learning and memory processes, neuroprotective effects such as anti-apoptosis and response to injury and inflammation, and neural ontogenetic functions on proliferation/differentiation processes from early stages.

Original languageEnglish (US)
Pages (from-to)423-439
Number of pages17
JournalCurrent Protein and Peptide Science
Volume3
Issue number4
DOIs
StatePublished - 2002

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Pituitary Adenylate Cyclase-Activating Polypeptide Receptors
Pituitary Adenylate Cyclase-Activating Polypeptide
Neurology
Nervous System
Vasoactive Intestinal Peptide
Neuropeptides
Adenylyl Cyclases
Receptors, Vasoactive Intestinal Peptide, Type II
Neurosecretion
Hypothalamic Hormones
Urochordata
Signal transduction
Circadian Clocks
Endocrine System
Secretin
Peripheral Nervous System
Neuroprotective Agents
Amphibians
Tissue Distribution
G-Protein-Coupled Receptors

ASJC Scopus subject areas

  • Biochemistry

Cite this

PACAP and its receptors exert pleiotropic effects in the nervous system by activating multiple signaling pathways. / Zhou, Chengji; Shioda, Seiji; Yada, Toshihiko; Inagaki, Nobuya; Pleasure, Samuel J.; Kikuyama, Sakae.

In: Current Protein and Peptide Science, Vol. 3, No. 4, 2002, p. 423-439.

Research output: Contribution to journalArticle

Zhou, Chengji ; Shioda, Seiji ; Yada, Toshihiko ; Inagaki, Nobuya ; Pleasure, Samuel J. ; Kikuyama, Sakae. / PACAP and its receptors exert pleiotropic effects in the nervous system by activating multiple signaling pathways. In: Current Protein and Peptide Science. 2002 ; Vol. 3, No. 4. pp. 423-439.
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