ADCYAP1R1 Membrane Protein Introduction

Introduction of ADCYAP1R1

ADCYAP1R1, also known as PACAP type I receptor or PACAP-R1, is a protein encoded by the human ADCYAP1R1 gene. It was first identified in 1994 as the receptor for the peptide hormone Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) which was discovered earlier as an adenylate cyclase stimulating agent in the ovine hypothalamus. Studies have shown that ADCYAP1R1, a membrane-associated protein, shares significant homology with members of the G-protein coupled class B glucagon receptor family.

Function of ADCYAP1R1 Membrane Protein

G-Protein Coupled Receptors (GPCRs) are important regulators of many physiological functions and have successfully attracted a lot of pharmacological interest for their roles in numerous diseases. It has been reported that ADCYAP1R1 plays important roles in several cellular processes, including regulation of circadian rhythm, control of food intake, glucose metabolism, learning and memory, neuronal ontogenesis, apoptosis, and immune system regulation. The expression of ADCYAP1R1 can be found in diverse tissues, such as adrenal medulla, pancreatic acini, uterus, myenteric plexus, and brain. It is also expressed in the trigeminal, otic and superior cervical ganglia (prejunctional) and cerebral arteries (postjunctional). Recently, studies have indicated that ADCYAP1R1 is implicated in post-traumatic stress disorder. What’s more, it is also upstream from the MAP-KK signaling system involved in cell cycle regulation. And the PAC1-R presents a potential novel target for small molecule drug discovery in the areas of neuroscience, oncology, and immunoscience.

Fig.1 A mechanism for postsynaptically expressed PACAP-induced synaptic enhancements in the BLA-CeL projections. (Cho, 2012)

Application of ADCYAP1R1 Membrane Protein in Literature

1. Tompkins J.D., et al. Src family kinase inhibitors blunt the PACAP-induced PAC1 receptor endocytosis, phosphorylation of ERK and increase in cardiac neuron excitability. American Journal of Physiology-Cell Physiology. 2017, 314(2): C233-C241. PubMed ID: 29141923
   
   

   This article reports that many cellular processes, including PAC1 receptor internalization, activation of MEK/ERK signaling, and regulation of neuronal excitability, are associated with the activity of the Src-related kinase. And the PAC1 receptor endosomal signaling plays a key role in regulating cellular function.

2. Girard B., et al. PACAP/receptor system in urinary bladder dysfunction and pelvic pain following urinary bladder inflammation or stress. Frontiers in systems neuroscience. 2017, 11:90. PubMed ID: 29255407
   
   

   This report reveals that the PACAP/PAC1 receptor system in micturition pathways may provide a potential target for therapeutic intervention to reduce LUT dysfunction.

3. Lind M.J., et al. Association of Posttraumatic Stress Disorder With rs2267735 in the ADCYAP1R1 Gene: A Meta-Analysis. Journal of traumatic stress. 2017, 30(4):389-98. PubMed ID: 28746747
   
   

   This article proves that there is an association between ADCYAP1R1 and PTSD. And the sex differences may exist.

4. Dragan W.Ł., et al. Pac1 receptor (ADCYAP1R1) genotype and problematic alcohol use in a sample of young women. Neuropsychiatric disease and treatment. 2017, 13:1483. PubMed ID: 28652748
   
   

   This article reveals that the PACAP/PAC1 signaling system is associated with the development of problematic alcohol use in women.

5. Mercer K.B., et al. Functional evaluation of a PTSD-associated genetic variant: estradiol regulation and ADCYAP1R1. Translational psychiatry. 2016, 6(12):e978. PubMed ID: 27959335
   
   

   This article suggests that estradiol (E2) could induce the expression of ADCYAP1R1 via binding of ERα at the ERE as an adaptive response to stress. And inhalation of E2/ERα binding to the ERE could reduce the expression of ADCYAP1R1 which acts as an adaptive stress response and increased risk for PTSD.

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Reference

1. Cho, et al. (2012). Pituitary adenylate cyclase-activating polypeptide induces postsynaptically expressed potentiation in the intra-amygdala circuit. Journal of Neuroscience. 32.41: 14165-14177.

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