Background of VIP/PACAP Receptors
The pituitary adenylate-cyclase-activating polypeptide (PACAP) is a neuropeptide that belongs to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. The high homology between PACAP and VIP allows them to share three common G protein-coupled receptors (GPCRs), including PAC1 receptor (PAC1R), VPAC1 receptor (VPAC1R), and VPAC2 receptor (VPAC2R). PACAP and its receptors are involved in a variety of biological functions in the peripheral and central nervous systems.
Fig.1. Molecular mechanism of VIP signal transduction. (Tang, 2014)
Distributions and Functions of VIP/PACAP Receptors
VPAC1R is distributed widely in the CNA, liver, lung, intestine, and T-lymphocytes, while the expression of VPAC2R can be detected in CNS, pancreas, skeletal muscle, heart, kidney, adipose tissue, testis, and stomach. PAC1R is predominantly expressed in the CNS, adrenal medulla, and pancreas. These receptors bind to both VIP and PACAP for further biological functions.
Subtypes and Mechanisms of VIP/PACAP Receptors
Based on their affinity for PACAP and VIP, PAC1R is classified into type 1 receptors, while VPAC1R and VPAC2R are classified into type II receptors, respectively.
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Receptor
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Gene
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Mechanism
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Agonists
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Antagonists
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Vasoactive intestinal peptide receptor 1
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VIPR1
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Vasoactive intestinal peptide receptor 1 is associated with AC through cAMP, and activates PKA and the mitogen-activated protein kinase (MAPK) pathway.
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VIP (6-28)
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[D-p-Cl-Phe6,Leu17]-VIP
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PG97-269
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Vasoactive intestinal peptide receptor 2
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VIPR2
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Vasoactive intestinal peptide receptor 2 is associated with AC through cAMP, and activates PKA and the mitogen-activated protein kinase (MAPK) pathway.
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VIP (6-28)
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[D-p-Cl-Phe6,Leu17]-VIP
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PACAP6-38
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ADCYAP receptor type I
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ADCYAP1R1
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ADCYAP receptor type 1 is associated with AC through cAMP, and activates PKA and the mitogen-activated protein kinase (MAPK) pathway.
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ADCYAP receptor type 1 couples to phospholipase C to stimulate Ca2+ mobilization and protein kinase C activation.
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Assay List of VIP/PACAP Receptors
Creative Biolabs can provide a range of assays of VIP/PACAP receptors. You can choose the assay in the list or contact us for more information:
VIPR1 VIPR2 ADCYAP1R1
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Assay No.
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Assay Name
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Host Cell
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Assay Type
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Datasheet
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cAMP Assay
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S01YF-0922-KX1452
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Magic™ Human VIPR1 In Vitro Agonist & Antagonist cAMP Assay
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HT-29
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cAMP Assay
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S01YF-0922-KX1456
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Magic™ Human VIPR1 In Vitro Agonist cAMP Assay
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CHO-K1
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cAMP Assay
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S01YF-0922-KX1460
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Magic™ Human VIPR1 In Vitro Antagonist cAMP Assay
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CHO-K1
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cAMP Assay
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S01YF-0922-KX1464
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Magic™ Human VIPR1 In Vitro PAM cAMP Assay
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CHO-K1
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cAMP Assay
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Calcium Flux Assay
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S01YF-0922-KX1455
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Magic™ Human VIPR1 In Vitro Agonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1459
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Magic™ Human VIPR1 In Vitro Antagonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1463
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Magic™ Human VIPR1 In Vitro PAM Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1466
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Magic™ Mouse VIPR1 In Vitro Agonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1468
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Magic™ Mouse VIPR1 In Vitro Antagonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1470
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Magic™ Mouse VIPR1 In Vitro PAM Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1472
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Magic™ Rat VIPR1 In Vitro Agonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1474
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Magic™ Rat VIPR1 In Vitro Antagonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1476
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Magic™ Rat VIPR1 In Vitro PAM Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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β-Arrestin Assay
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S01YF-0922-KX1454
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Magic™ Human VIPR1 In Vitro Agonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1458
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Magic™ Human VIPR1 In Vitro Antagonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1462
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Magic™ Human VIPR1 In Vitro PAM β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1465
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Magic™ Mouse VIPR1 In Vitro Agonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1467
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Magic™ Mouse VIPR1 In Vitro Antagonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1469
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Magic™ Mouse VIPR1 In Vitro PAM β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1471
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Magic™ Rat VIPR1 In Vitro Agonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1473
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Magic™ Rat VIPR1 In Vitro Antagonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1475
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Magic™ Rat VIPR1 In Vitro PAM β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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Internalization Assay
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S01YF-0922-KX1453
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Magic™ Human VIPR1 In Vitro Agonist Internalization Assay
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U2OS
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Internalization Assay
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S01YF-0922-KX1457
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Magic™ Human VIPR1 In Vitro Antagonist Internalization Assay
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U2OS
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Internalization Assay
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S01YF-0922-KX1461
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Magic™ Human VIPR1 In Vitro PAM Internalization Assay
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U2OS
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Internalization Assay
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Radioligand Binding Assay
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S01YF-0722-KX418
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Magic™ Human VIPR1 In Vitro Agonist Radioligand Binding Assay
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Radioligand Binding Assay
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Assay No.
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Assay Name
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Host Cell
|
Assay Type
|
Datasheet
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|
cAMP Assay
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|
S01YF-0922-KX1479
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Magic™ Human VIPR2 In Vitro Agonist cAMP Assay
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CHO-K1
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cAMP Assay
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S01YF-0922-KX1483
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Magic™ Human VIPR2 In Vitro Antagonist cAMP Assay
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CHO-K1
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cAMP Assay
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S01YF-0922-KX1487
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Magic™ Human VIPR2 In Vitro PAM cAMP Assay
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CHO-K1
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cAMP Assay
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Calcium Flux Assay
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S01YF-0922-KX1478
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Magic™ Human VIPR2 In Vitro Agonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1482
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Magic™ Human VIPR2 In Vitro Antagonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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S01YF-0922-KX1486
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Magic™ Human VIPR2 In Vitro PAM Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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β-Arrestin Assay
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S01YF-0922-KX1477
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Magic™ Human VIPR2 In Vitro Agonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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S01YF-0922-KX1481
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Magic™ Human VIPR2 In Vitro Antagonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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|
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S01YF-0922-KX1485
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Magic™ Human VIPR2 In Vitro PAM β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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|
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Internalization Assay
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S01YF-0922-KX1480
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Magic™ Human VIPR2 In Vitro Agonist Internalization Assay
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U2OS
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Internalization Assay
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S01YF-0922-KX1484
|
Magic™ Human VIPR2 In Vitro Antagonist Internalization Assay
|
U2OS
|
Internalization Assay
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S01YF-0922-KX1488
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Magic™ Human VIPR2 In Vitro PAM Internalization Assay
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U2OS
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Internalization Assay
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Radioligand Binding Assay
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S01YF-0722-KX419
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Magic™ Human VIPR2 In Vitro Agonist Radioligand Binding Assay
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Radioligand Binding Assay
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Assay No.
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Assay Name
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Host Cell
|
Assay Type
|
Datasheet
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|
cAMP Assay
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S01YF-0922-KX1082
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Magic™ Human ADCYAP1R1 In Vitro Agonist & Antagonist cAMP Assay
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CHO-K1
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cAMP Assay
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S01YF-0922-KX1085
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Magic™ Human ADCYAP1R1 In Vitro Agonist cAMP Assay
|
CHO-K1
|
cAMP Assay
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S01YF-0922-KX1089
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Magic™ Human ADCYAP1R1 In Vitro Antagonist cAMP Assay
|
CHO-K1
|
cAMP Assay
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|
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S01YF-0922-KX1093
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Magic™ Human ADCYAP1R1 In Vitro PAM cAMP Assay
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CHO-K1
|
cAMP Assay
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|
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Calcium Flux Assay
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S01YF-0922-KX1084
|
Magic™ Human ADCYAP1R1 In Vitro Agonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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|
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S01YF-0922-KX1088
|
Magic™ Human ADCYAP1R1 In Vitro Antagonist Calcium Flux Assay
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CHO-K1
|
Calcium Flux Assay
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|
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S01YF-0922-KX1092
|
Magic™ Human ADCYAP1R1 In Vitro PAM Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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|
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S01YF-0922-KX1096
|
Magic™ Mouse ADCYAP1R1 In Vitro Agonist Calcium Flux Assay
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CHO-K1
|
Calcium Flux Assay
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|
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S01YF-0922-KX1098
|
Magic™ Mouse ADCYAP1R1 In Vitro Antagonist Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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|
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S01YF-0922-KX1100
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Magic™ Mouse ADCYAP1R1 In Vitro PAM Calcium Flux Assay
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CHO-K1
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Calcium Flux Assay
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β-Arrestin Assay
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S01YF-0922-KX1083
|
Magic™ Human ADCYAP1R1 In Vitro Agonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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|
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S01YF-0922-KX1087
|
Magic™ Human ADCYAP1R1 In Vitro Antagonist β-Arrestin Assay
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CHO-K1
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β-Arrestin Assay
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|
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S01YF-0922-KX1091
|
Magic™ Human ADCYAP1R1 In Vitro PAM β-Arrestin Assay
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CHO-K1
|
β-Arrestin Assay
|
|
|
S01YF-0922-KX1095
|
Magic™ Mouse ADCYAP1R1 In Vitro Agonist β-Arrestin Assay
|
CHO-K1
|
β-Arrestin Assay
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|
|
S01YF-0922-KX1097
|
Magic™ Mouse ADCYAP1R1 In Vitro Antagonist β-Arrestin Assay
|
CHO-K1
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β-Arrestin Assay
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|
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S01YF-0922-KX1099
|
Magic™ Mouse ADCYAP1R1 In Vitro PAM β-Arrestin Assay
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CHO-K1
|
β-Arrestin Assay
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|
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Internalization Assay
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S01YF-0922-KX1086
|
Magic™ Human ADCYAP1R1 In Vitro Agonist Internalization Assay
|
U2OS
|
Internalization Assay
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|
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S01YF-0922-KX1090
|
Magic™ Human ADCYAP1R1 In Vitro Antagonist Internalization Assay
|
U2OS
|
Internalization Assay
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|
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S01YF-0922-KX1094
|
Magic™ Human ADCYAP1R1 In Vitro PAM Internalization Assay
|
U2OS
|
Internalization Assay
|
|
|
Radioligand Binding Assay
|
|
S01YF-0722-KX405
|
Magic™ Human ADCYAP1R1 In Vitro Agonist Radioligand Binding Assay
|
|
Radioligand Binding Assay
|
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Published Data
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Paper Title
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Signal Transduction by VIP and PACAP Receptors
|
|
Journal
|
Biomedicines
|
|
Published
|
2022
|
|
Abstract
|
The homeostasis of the human immune system is regulated by two neuropeptides, VIP and PACAP. These two neuropeptides can regulate intestinal motility and secretion, and affect the function of the endocrine & immune systems. Inhibition of VIP and PACAP receptors has therefore been investigated for new drug therapies in chronic inflammation and cancer. In this paper, we describe VPAC1, VPAC2, and PAC1 as triggers for receptor activation and compare them to similar noncovalent interactions observed for other GPCRs upon activation. The interaction between VIP and PACAP receptors provides a molecular basis for the development of anti-inflammatory, anti-cancer, and neuroprotective drugs. In addition, we also examined the effect of genetic variants of VIP, PACAP, and their receptors on endogenous agonist-mediated signaling.
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Result
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VIP and PACAP receptor signaling is of high complexity. The weak selectivity of endogenous agonists has somewhat hampered the therapeutic application of VPAC and PAC1 receptors in endocrine, metabolic, anti-inflammatory, and anticancer treatments. Recently, the discovery of the first small-molecule negative allosteric modulator provides new ideas for drug repositioning screening. The cryo-EM structures of VPAC1 and PAC1 also provided a conformational basis. In this paper, we have verified that the VIP/PACAP receptor signaling pathway was associated with the regulation of excessive inflammatory responses and provided a new approach for the treatment of chronic autoimmune diseases and acute inflammation.
 Fig.2. VIP and PACAP receptor-mediated signaling pathways. (Langer, et al., 2022)
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References
-
Tang, B.; et al. Vasoactive intestinal peptide receptor-based imaging and treatment of tumors. International journal of oncology. 2014, 44(4): 1023-1031.
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Langer, I.; et al. Signal transduction by VIP and PACAP receptors. Biomedicines. 2022, 10(2): 406.
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