Effector coupling of somatostatin receptor subtypes on human endocrine tumors

Abstract 

Effector coupling of somatostatin receptor subtypes sst₁ and sst₂ was examined in a reconstituted system. Forskolin-stimulated cyclic adenosine monophosphate (cAMP) formation was inhibited 66% by somatostatin (SRIF-14) in CHO cells expressing somatostatin receptor 1 (sst₁) (CHO-SR1), but not sst₂, in a dose-dependent manner with an ED₅₀ of 1 × 10⁻⁹ mol/L SRIF-14. The inhibition was blocked by pertussis toxin (PTX), indicating that sst₁ is coupled to adenylyl cyclase via PTX-sensitive G_i protein. In CHO cells, G_iα2 and G_iα3 mRNAs were detected. In adenylyl cyclase assays, 1 μmol/L SRIF-14 caused a 16% inhibition of forskolin-stimulated adenyly cyclase activity. Preincubation with G_iα3, but not , antiserum blocked this inhibition. By contrast, sst₂ is coupled to adenylyl cyclase via G_iα1. In cells expressing sst₂ with G_iα1 (CHO-SR2G1), SRIF-14 significantly inhibited forskolin-stimulated cAMP formation by 53% and with an ED₅₀ at 4 × 10⁻⁹ mmol/L SRIF-14, which was completely blocked by PTX; ED₅₀ values for sst₁ and sst₂ agree with the IC₅₀ values in binding assays. In CHO-SR1, the rank of potency of agonists affecting adenyl cyclase was SRIF-14 = SRIF-28 > RC 160 > SMS 201-995. In CHO-SR2G1, the rank was RC-160 > SRIF-14 = SRIF-28 > SMS201-995.

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