Multiple effector coupling of somatostatin receptor subtype SSTR1.
The signal transduction pathways of a cloned human somatostatin receptor subtype, SSTR1, have been investigated in CHO cells stably expressing this receptor. In SSTR1-expressing CHO cells, somatostatin-14 inhibits forskolin-stimulated cAMP formation in a dose-dependent manner with an ED50 of 1.0 x 10(-9) M. Somatostatin-14 also stimulates inositol 1,4,5-trisphosphate formation in a dose-dependent manner with an ED50 of 4.0 x 10(-8) M. Somatostatin-14 inhibitory action on adenylyl cyclase and stimulatory action on inositol 1,4,5-trisphosphate formation are both blocked by pertussis toxin, indicating that these effects of SSTR1 are mediated by pertussis toxin-sensitive G protein(s). Antiserum against Gi alpha 3 blocked the inhibitory effects of somatostatin-14 on forskolin-stimulated adenylyl cyclase, but antiserum against Gi alpha 1/Gi alpha 2 did not, indicating that Gi alpha 3 dominantly couples SSTR1 to adenylyl cyclase. These results demonstrate that SSTR1 can be coupled to different signaling pathways to exert multiple biological effects, one of which is mediated by Gi alpha 3.
Kubota
A
A
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan.
Yamada
Y
Y
Kagimoto
S
S
Yasuda
K
K
Someya
Y
Y
Ihara
Y
Y
Okamoto
Y
Y
Kozasa
T
T
Seino
S
S
Seino
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D012313:RNA / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000096:biosynthesis* / Q000145:classification / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D014162:Transfection
D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D005576:Colforsin; D016718:Arachidonic Acid; C051458:vapreotide; D013004:Somatostatin; D012313:RNA; D002217:Carbachol; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases