Molecular Cloning and Functional Expression of Rat cDNAs Encoding the Receptor for Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)

Hashimoto, Masaki; Onda, Haruo; Ogi, Kazuhiro; Masuda, Yasushi; Miyamoto, Yasunori; Ohtaki, Tetsuya; Okazaki, H.; Arimura, Akira; Fujino, Masahiko

doi:10.1006/bbrc.1993.1795

Cited by 152 publications

(54 citation statements)

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“…This PAC1-R cDNA, which encodes a 495-amino acid protein with seven putative membrane spanning domains, exhibits a high degree of sequence identity with the glucagon, secretin, and calcitonin receptor cDNAs. PAC1-R have subsequently been cloned in human , bovine (Miyamoto et al, 1994), rat (Hashimoto et al, 1993;Hosoya et al, 1993;Morrow et al, 1993;Spengler et al, 1993;Svoboda et al, 1993), and mouse (Hashimoto et al, 1996b). The PAC1-R has also been cloned in several nonmamalian species Alexandre et al, 1999;Hu et al, 2000;Cardoso et al, 2007b).…”

Section: Cloning Of Pituitary Adenylate Cyclase-activating Polypepmentioning

confidence: 99%

“…In the rat ovary, the presence of PAC1-R and VPAC2-R mRNAs has been reported (Usdin et al, 1994;Scaldaferri et al, 1996;Kotani et al, 1997Kotani et al, , 1998. Granulosa cells of the developing follicle express VPAC2-R mRNA (Usdin et al, 1994), whereas the corpus luteum contains PAC1-R Hosoya et al, 1993;Usdin et al, 1994;Chatterjee et al, 1996;Pei, 1997 Delgado et al, 1996c,d;Ganea, 1996;Johnson et al, 1996 The symbols provide a semi-quantitative evaluation of the density of PAC1-R, VPAC1-R and VPAC2-R mRNA. ϩϩϩ, high density; ϩϩ, moderate density; ϩ, low density; -, no hybridization.…”

Section: F Distribution Of Pituitary Adenylate Cyclaseactivating Polmentioning

confidence: 99%

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Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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Section: Cloning Of Pituitary Adenylate Cyclase-activating Polypepmentioning

confidence: 99%

Section: F Distribution Of Pituitary Adenylate Cyclaseactivating Polmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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“…Two forms can be distinguished, PACAP-38 and a truncated product PACAP-27, both of which are derived from a 176 precursor protein (19.5 kDa) by posttranslational cleavage (349). The mature peptide has a molecular mass of ϳ5 kDa.…”

Section: Pacapmentioning

confidence: 99%

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Roosterman¹,

Goerge

Schneider

et al. 2006

Physiological Reviews

556

521

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This review focuses on the role of the peripheral nervous system in cutaneous biology and disease. During the last few years, a modern concept of an interactive network between cutaneous nerves, the neuroendocrine axis, and the immune system has been established. We learned that neurocutaneous interactions influence a variety of physiological and pathophysiological functions, including cell growth, immunity, inflammation, pruritus, and wound healing. This interaction is mediated by primary afferent as well as autonomic nerves, which release neuromediators and activate specific receptors on many target cells in the skin. A dense network of sensory nerves releases neuropeptides, thereby modulating inflammation, cell growth, and the immune responses in the skin. Neurotrophic factors, in addition to regulating nerve growth, participate in many properties of skin function. The skin expresses a variety of neurohormone receptors coupled to heterotrimeric G proteins that are tightly involved in skin homeostasis and inflammation. This neurohormone-receptor interaction is modulated by endopeptidases, which are able to terminate neuropeptide-induced inflammatory or immune responses. Neuronal proteinase-activated receptors or transient receptor potential ion channels are recently described receptors that may have been important in regulating neurogenic inflammation, pain, and pruritus. Together, a close multidirectional interaction between neuromediators, high-affinity receptors, and regulatory proteases is critically involved to maintain tissue integrity and regulate inflammatory responses in the skin. A deeper understanding of cutaneous neuroimmunoendocrinology may help to develop new strategies for the treatment of several skin diseases.

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“…The actions of PACAP are mediated through G-protein-coupled receptors (GPCRs) that belong to group II of the secretin receptor family. Three PACAP/vasoactive intestinal polypeptide (VIP) receptor genes have been cloned: one encodes the PACAP-preferring receptor PAC1 (Hashimoto et al, 1993;Hosoya et al, 1993;Morrow et al, 1993;Pisegna and Wank, 1993;Spengler et al, 1993;Aino et al, 1995;Vaudry et al, 2000;Harmar, 2001), whereas the other two encode receptors that respond equally to PACAP and VIP (VPAC1 and VPAC2) (Ishihara et al, 1992;Lutz et al, 1993Lutz et al, , 1999. Typically, group II receptors signal through the protein kinase A (PKA) pathway, although PAC1 not only activates the PKA pathway but is also coupled to the phospholipase C (PLC) pathway, resulting in changes in the intracellular calcium concentration ([Ca 2ϩ ] i ).…”

Section: Introductionmentioning

confidence: 99%

Differential Intracellular Signaling through PAC1 Isoforms as a Result of Alternative Splicing in the First Extracellular Domain and the Third Intracellular Loop

Ushiyama

Ikeda²,

Sugawara³

et al. 2007

Mol Pharmacol

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Pituitary adenylate cyclase-activating polypeptide (PACAP), a pleiotropic neuropeptide, performs a variety of physiological functions. The PACAP-specific receptor PAC1 has several variants that result mainly from alternative splicing in the mRNA regions encoding the first extracellular (EC1) domain and the third intracellular cytoplasmic (IC3) loop. The effects on downstream signaling produced by combinations of alternative splicing events in the EC1 domain and IC3 loop have not yet been clarified. In this study, we have used semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to examine the tissue distributions of four PAC1 isoforms in mice. We then established cell lines constitutively expressing each of the PAC1 isoforms and characterized the binding properties of each isoform to PACAP-38, vasoactive intestinal polypeptide (VIP), and the PAC1-specific agonist maxadilan, as well as the resulting effects on two major intracellular signaling pathways: cAMP production and changes in the intracellular calcium concentration. The results demonstrate that the variants of the IC3 loop affect the binding affinity of the ligands for the receptor, whereas the variants of the EC1 domain primarily affect the intracellular signaling downstream of PAC1. Accordingly, this study indicates that the combination of alternative splicing events in the EC1 domain and the IC3 loop create a variety of PAC1 isoforms, which in turn may contribute to the functional pleiotropism of PACAP. This study not only contributes to the understanding of the multiple functions of PACAP but also helps to elucidate the relationship between the structures and functions of G-protein-coupled receptors.Pituitary adenylate cyclase-activating polypeptide (PACAP), a pleiotropic neuropeptide first isolated from ovine hypothalamus, occurs in two forms: one consists of 38 amino acid residues (PACAP-38) and the other contains 27 amino acid residues (PACAP-27) (Miyata et al., 1989. The actions of PACAP are mediated through G-protein-coupled receptors (GPCRs) that belong to group II of the secretin receptor family. Three PACAP/vasoactive intestinal polypeptide (VIP) receptor genes have been cloned: one encodes the PACAP-preferring receptor PAC1 (Hashimoto et al., 1993;Hosoya et al., 1993;Morrow et al., 1993;Pisegna and Wank, 1993;Spengler et al., 1993;Aino et al., 1995;Vaudry et al., 2000;Harmar, 2001), whereas the other two encode receptors that respond equally to PACAP and VIP (VPAC1 and VPAC2) (Ishihara et al., 1992;Lutz et al., 1993Lutz et al., , 1999. Typically, group II receptors signal through the protein kinase A (PKA) pathway, although PAC1 not only activates the PKA pathway but is also coupled to the phospholipase C (PLC) pathway, resulting in changes in the intracellular calcium concentration ([Ca 2ϩ ] i ). In mice, the PAC1 gene contains more than 18 exons, and more splice variants of PAC1 have been identified than for most of the other GPCRs (Aino et al., 1995). Most of the PAC1 isoforms are formed as a result of altern...

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Molecular Cloning and Functional Expression of Rat cDNAs Encoding the Receptor for Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)

Cited by 152 publications

References 0 publications

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

Differential Intracellular Signaling through PAC1 Isoforms as a Result of Alternative Splicing in the First Extracellular Domain and the Third Intracellular Loop

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