Heterodimerization of β2 adrenergic receptor and somatostatin receptor 5: Implications in modulation of signaling pathway

Background: In the present study, we describe heterodimerization between human-Somatostatin Receptor 5 (hSSTR5) and β₂-Adrenergic Receptor (β₂AR) and its impact on the receptor trafficking, coupling to adenylyl cyclase and signaling including mitogen activated protein kinases and calcineurin-NFAT pathways.

Methods: We used co-immunoprecipitation, photobleaching- fluorescence resonance energy transfer and Fluorescence assisted cell sorting analysis to characterize heterodimerization between SSTR5 and b2AR.

Results: Our results indicate that hSSTR5/β₂AR exist as preformed heterodimers in the basal condition which is enhanced upon co-activation of both receptors. In contrast, the activation of individual receptors leads to the dissociation of heterodimers. Receptor coupling to adenylyl cyclase displayed predominant effect of β₂AR, however, somatostatin mediated inhibition of cAMP was enhanced upon blocking β₂AR. Our results indicate hSSTR5 mediated significant activation of ERK1/2 and inhibition of phospho-p38. The phospho-NFAT level was enhanced in cotransfected cells indicating the blockade of calcineurin mediated dephosphorylation of NFAT upon receptor heterodimerization.

Conclusion: These data for the first time unveil a novel insight for the role of hSSTR5/β₂AR in the modulation of signaling pathways which has not been addressed earlier.