Objective: To investigate whether mechanical stretch is associated with μ-opioid and somatostatin receptor (SSTR) dimerization in cardiomyocytes and if such dimerization is mediated via endogenous opioids, somatostatin (SST) and/or angiotensin II. Method: Using a well-established cyclic mechanical stretch model exerting strain on primary cultured neonatal Wistar rat cardiomyocytes, we studied the changes of homo-or hetero-dimerization of SSTR-2A and/or μ-opioid receptor (MOR-1) of cardiomyocyte under such stress. Western blot and immunoprecipitation were utilized to demonstrate the related changes. The effects of opioids and SST on SSTR/MOR1 dimer expression were investigated by specific agonists such as SST-14 and DAMGO. The role of endogenous angiotensin II was also studied by applying losartan to test the effects of AT-1 receptor blockade.
Results: Our data have shown that 6h mechanical stretch could activate both homo-dimerization of SST2A and MOR1 as well as hetero-dimerization of SST2A/MOR1. Neither SST-14 nor DAMGO exerted significant effects on homo-and hetero-dimerization of SST2A/MOR1 during mechanical stress, whereas losartan could attenuate significantly formation of SST2A / MOR homo- and hetero-dimers, demonstrating the role of endogenous angiotensin II. Conclusion: This study demonstrated that mechanical stretch could accentuate SST2A/MOR1 homo- and hetero-dimerization in an endogenous angiotensin II-dependent manner.