Structural and Pharmacological Characterisation of Splice Isoforms of the Pituitary Adenylate Cyclase-Activating Polypeptide Type 1 (PAC1) Receptor

The pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1R) is a promising drug target for the treatment of numerous central nervous system disorders where there is significant unmet clinical need. This may, in part, be due to the existence of multiple PAC1R splice isoforms, from alternative splicing in the N-terminal extracellular domain (ECD) and intracellular loop 3 (ICL3) regions. These regions may be important for ligand recognition and transducer coupling and activation of PAC1R, hence the pharmacological profiles of the N-terminal ECD and ICL3 PAC1R splice isoforms and structural determinants of select PAC1R N-terminal ECD splice isoforms were investigated.