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Mol Pharmacol

Title:		Identification and characterization of novel somatostatin antagonists
Author(s):		Bass RT; Buckwalter BL; Patel BP; Pausch MH; Price LA; Strnad J; Hadcock JR;
Address:		"Cyenamid Agricultural Research Center, Princeton, NJ 08543-0400, USA"
Journal Title:		Mol Pharmacol
Year:		1996
Volume:		50
Issue:		4
Page Number:		709 - 715
DOI:
ISSN/ISBN:		0026-895X (Print) 0026-895X (Linking)
Abstract:		"The study of the five somatostatin receptor subtypes (SSTx, where x is the subtype number) has been hampered by the lack of high affinity antagonists. Potent and selective antagonists would increase our understanding of SST structure, function, and regulation. In this study, the identification of novel disulfide-linked cyclic octapeptide antagonists of somatostatin is described. The antagonists contain a core structure of a DL-cysteine pair at positions 2 and 7 of the peptides. Substitution of a D-cysteine at position 2 with an L-cysteine converts the full antagonist into a full agonist. All somatostatin receptor subtypes are coupled to inhibition of adenylate cyclase. The functional properties of these peptides have been determined in radioligand binding assays, in functional coupling of the SST2 subtype to yeast pheromone response pathway, and in cAMP accumulations. One peptide antagonist [Ac-4-NO2-Phe-c(D-Cys-Tyr-D-Trp-Lys-Thr-Cys)-D-Tyr-NH2] displays a binding affinity to SST2 comparable with that observed for the native hormone (Ki = 0.2 nM) and reverses somatostatin-mediated inhibition of cAMP accumulation in rat somatomammotroph GH4C1 cells, cells transfected with the SST2 and SST5 subtypes, as well as somatostatin-stimulated growth of yeast cells expressing the SST2 subtype. This class of somatostatin antagonists, which are the first to be described, should be useful for determination of somatostatin's diverse functions in vivo and in vitro"
Keywords:		"Amino Acid Sequence Animals Binding, Competitive Cyclic AMP/metabolism Iodine Radioisotopes Peptides/metabolism/pharmacology Radioligand Assay Rats Receptors, Somatostatin/antagonists & inhibitors/metabolism Saccharomyces cerevisiae/drug effects Somatosta;"
Notes:		"MedlineBass, R T Buckwalter, B L Patel, B P Pausch, M H Price, L A Strnad, J Hadcock, J R eng 1996/10/01 Mol Pharmacol. 1996 Oct; 50(4):709-15"