Different G proteins mediate somatostatin-induced inward rectifier K+ currents in murine brain and endocrine cells

1. Types of G proteins (G protein alpha-subunit subtypes) which mediate the activation of inward rectifier K+ currents by somatostatin (somatotrophin release-inhibiting factor, SRIF) were determined in cultured locus coeruleus neurones from newborn rats and in AtT-20 cells (a mouse pituitary cell line). 2. The whole-cell patch clamp technique was used together with injection of antibodies against pertussis toxin (PTX)-sensitive G protein alpha-subunits or with injection of antisense (or sense) oligonucleotides against these G proteins. 3. In locus coeruleus neurones, the SRIF-induced activation of inward rectifier K+ currents was inhibited by anti-G alpha i1/G alpha i2 antibody injection, but not by anti-G alpha i3 or by anti-G alpha o/G alpha i3 antibody injection, suggesting that the SRIF response is mediated through G alpha i1 and/or G alpha i2. 4. The SRIF-induced activation of the inward rectifier was suppressed in locus coeruleus neurones after injection of antisense oligonucleotides against G alpha i2, but not by injection of sense oligonucleotides against G alpha i2. Injection of antisense (or sense) oligonucleotides against G alpha i1, G alpha i3 and G alpha O (common) had no effect. These results suggest that G alpha i2 is involved in this SRIF response. 5. In AtT-20 cells, the SRIF-induced activation of inward rectifier K+ currents was suppressed by injection of anti-G alpha i3 antibody, but not by injection of anti-G alpha i1/G alpha i2 antibody. 6. The above results indicate that Gi mediates the SRIF effects on inward rectifier K+ currents. However, different subtypes of Gi are involved in the brain neurones and in the endocrine cells: Gi2 in locus coeruleus neurones and Gi3 in AtT-20 cells.