Target intelligence / Profile preview

Pituitary Adenylate Cyclase-Activating Polypeptide Receptor PAC1 (PAC1R)

Target
PAC1R
Molecular classification
G protein-coupled receptor, GPCR, Class B GPCR, Receptor
01

Overview

The pituitary adenylate cyclase-activating polypeptide receptor PAC1 (PAC1R) is a G protein-coupled receptor that binds PACAP with high affinity. It belongs to the class B family of GPCRs and undergoes extensive alternative splicing, resulting in several isoforms with differing signaling properties. PAC1R is widely expressed throughout the central and peripheral nervous systems, as well as endocrine tissues, and plays a role in diverse physiological functions, including neuroendocrine regulation, stress response, and pain processing. Dysregulation of the PACAP/PAC1 system is implicated in psychiatric conditions like PTSD and chronic pain states such as migraine headaches.

Other names
ADCYAP receptor type 1Adenylate cyclase activating polypeptide 1 receptor 1Pituitary adenylate cyclase activating polypeptide type I receptorPVR1PACAPRPACAP type IA receptor
02

Mechanism of action

Agonist binding leads to activation of Gs and Gq proteins, increasing cAMP and intracellular calcium levels, respectively. This further activates downstream signaling pathways such as PKA, PKC and ERK.

03

Biological functions

Signal transductionNeuroendocrine hormone synthesis/release regulationCell proliferation/differentiation/survival modulationStress response modulationModulation of ionic currentscAMP productionCalcium signaling
04

Disease associations

Anxiety disorders (e.g., PTSD)MigraineChronic painNeurodegenerative disease (potential protective roles)Immune system dysregulation
05

Safety considerations

Potential for off-target effects due to widespread tissue distributionComplex signaling pathways may lead to unpredictable effects

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