![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
JR Hadcock, J Strnad and CM Eppler
Molecular and Cellular Biology Group, American Cyanamid Company, Princeton, New Jersey 08543-0400.
The pharmacology, signal transduction, and coupling to G proteins of the rat somatostatin (SRIF) receptor (SSTR)1 have been characterized in transfected Chinese hamster ovary (CHO) (K1 strain) cells. The expressed receptor exhibited saturable, high affinity binding of several radioiodinated SRIF analogues. Three different radioligands were used to determine the pharmacological properties of this SSTR subtype. [125I-Tyr11]SRIF-14 (125I-S-14), [Leu8,D-Trp22,125I-Tyr25]SRIF- 28 (125I-S-28), and cyclo(D-Trp-Lys-Abu-Phe-MeAla-125I-Tyr) (125I- peptide C) displayed the following rank order of affinity (Kd) for the SSTR1 subtype: 125I-S-14 > or = 125I-S-28 > 125I-peptide C. Competition of 125I-S-14 with S-14, S-28, or peptide C displayed the same rank order of potency. Chemical cross-linking of specifically bound 125I-S- 28 to membranes from CHO cells expressing the receptor indicated that the molecular weight of the SSTR1 expressed in CHO cells is approximately 70,000, suggesting that it is heavily glycosylated. Previous reports have suggested that the human SSTR1 [Mol. Pharmacol. 42:28-34 (1992)] couples poorly to G proteins. The coupling of the rat SSTR1 to G proteins was demonstrated by three independent methods. (a) Binding of 125I-S-14 to the SSTR1 subtype was inhibited in a dose- dependent fashion by incubation of membranes with guanosine-5'-O-(3- thio)triphosphate. (b) Treatment of cells with pertussis toxin decreased binding by 80%. (c) Immunoprecipitation of 125I-S-14 binding was observed with antiserum specific for Gi alpha 1,2, but not with antiserum specific for Gs alpha, in membranes from transfected cells. In CHO cells transfected with the SSTR1 cDNA, SRIF inhibited forskolin- stimulated cAMP accumulation by up to 50%, in a dose-dependent fashion (ED50 = 1.1 nM). Pertussis toxin treatment decreased both the efficacy and the potency of the SRIF-mediated inhibition of cAMP accumulation (from 50% to 22%), compared with control untreated cells. These data suggest that the rat SSTR1 inhibits cAMP accumulation by coupling to pertussis toxin-sensitive G proteins.
This article has been cited by other articles:
|
|
 |
|
  J. A. Grodnitzky, N. Syed, M. J. Kimber, T. A. Day, J. G. Donaldson, and W. H. Hsu Somatostatin Receptors Signal through EFA6A-ARF6 to Activate Phospholipase D in Clonal beta-Cells J. Biol. Chem., May 4, 2007; 282(18): 13410 - 13418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-J. Zhu, K. Krempels, C. W. Bardin, A.-M. O'Carroll, and E. Mezey The Localization of Messenger Ribonucleic Acids for Somatostatin Receptors 1, 2, and 3 in Rat Testis Endocrinology, January 1, 1998; 139(1): 350 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Murthy, D. H. Coy, and G. M. Makhlouf Somatostatin Receptor-mediated Signaling in Smooth Muscle. ACTIVATION OF PHOSPHOLIPASE C-beta 3 BY Gbeta gamma AND INHIBITION OF ADENYLYL CYCLASE BY Galpha i1 AND Galpha o J. Biol. Chem., September 20, 1996; 271(38): 23458 - 23463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hayashida, M. Horiuchi, and V. J. Dzau Intracellular Third Loop Domain of Angiotensin II Type-2 Receptor. ROLE IN MEDIATING SIGNAL TRANSDUCTION AND CELLULAR FUNCTION J. Biol. Chem., September 6, 1996; 271(36): 21985 - 21992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Liu and A. Schonbrunn Agonist-induced Phosphorylation of Somatostatin Receptor Subtype 1 (Sst1). RELATIONSHIP TO DESENSITIZATION AND INTERNALIZATION J. Biol. Chem., January 26, 2001; 276(5): 3709 - 3717. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
