NDLI: Alternative Splicing of the Pituitary Adenylate Cyclase-activating Polypetide (PACAP) Receptor Contributes to Function of PACAP-27

Content Provider	Springer Nature Link
Author	Ushiyama, Mina Ikeda, Ryuji Yoshida, Morikatsu Mori, Kenji Kangawa, Kenji Sugawara, Hideki Iue, Kazuhiko Yamada, Katsushi Miyata, Atsuro
Copyright Year	2010
Abstract	Pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 are neuropeptides performing a variety of physiological functions. The PACAP-specific receptor PAC1 has several variants that result mainly from alternative splicing in the mRNA region encoding the first extracellular (EC1) domain and the third intracellular cytoplasmic (IC3) loop. To characterize the molecular forms of alternative splicing variants of PAC1, we examined the binding affinity and activation of two major second messenger pathways (cAMP production and changes in [Ca$^{2+}$]$_{i}$) by PACAP-27. Activation of cAMP was influenced by the variant in both of the EC1 domain and IC3 loops. In the N form in the EC1 domain, the suppressive effect of the HOP1 form in the IC3 loop was enhanced. Regarding the intracellular calcium mobilization assay, the rank order of the potency of PACAP-27 for the different PAC1 isoforms was S/HOP1 >> N/R ≅ S/R >> N/HOP1. In particular, PACAP-27 exhibited remarkable potency of calcium mobilization in the S/HOP1-expressing cells at sub-picomolar concentrations even though the affinities of PACAP-27 to the four PAC1 isoforms were not significantly different. This suggests the specific functions of PACAP-27 due to PACAP-27 preferring PAC1 activation, and leads in clarification of the pleiotoropic function of PACAP.
Starting Page	341
Ending Page	348
Page Count	8
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	42
Issue Number	3
e-ISSN	15591166
Language	English
Publisher	Humana Press Inc
Publisher Date	2010-05-15
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	PACAP-27 Intracellular calcium concentration cAMP Binding affinity PAC1 PACAP-specific receptor Neurology Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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