title: Splice variant of the somatostatin receptor 2 subtype, somatostatin receptor 2B, couples to adenylyl cyclase.
abstract: The diverse biological actions of somatostatin (SRIF) are mediated by a family of receptors, of which five have been cloned and characterized. One of the SRIF receptor subtypes, SSTR2, has been shown to exist in two forms. SSTR2A and SSTR2B are 369 and 346 amino acids in size, respectively, and differ in length and amino acid sequence in their intracellularly located carboxyl termini. SSTR2A and SSTR2B are generated by alternative splicing of SSTR2 mRNA. We previously characterized mouse SSTR2A and showed that it could be distinguished from other cloned SRIF receptor subtypes by its high affinity for MK-678 and its lack of coupling to adenylyl cyclase. To determine whether the properties of mouse SSTR2A and SSTR2B differ, we have expressed both in COS-7 cells and characterized their ligand-binding properties and ability to couple to adenylyl cyclase. The two receptors exhibited similar affinities for a number of SSTR2-selective agonists such as MK-678. Pretreatment with SRIF of COS-7 cells expressing each receptor reduced high affinity agonist binding to both SSTR2A and SSTR2B, indicating that both receptors can be regulated. Furthermore, agonist binding to both receptors was reduced by GTP analogs and Na+, indicating that they both associate with G proteins. As shown previously, SSTR2A could not mediate SRIF inhibition of forskolin-stimulated cAMP formation. In contrast, SSTR2B was coupled to adenylyl cyclase and was able to mediate SRIF inhibition of forskolin-stimulated cAMP formation. Thus, SSTR2A and SSTR2B differ in their ability to couple to adenylyl cyclase. Because SSTR2A and SSTR2B differ only in the length and amino acid sequence of their carboxyl termini, these findings imply that the carboxyl-terminal 15 residues of SSTR2B may be involved in coupling this receptor to adenylyl cyclase.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: T
authors.initials: T
authors.lastname: Reisine
authors.forename: H
authors.initials: H
authors.lastname: Kong
authors.forename: K
authors.initials: K
authors.lastname: Raynor
authors.forename: H
authors.initials: H
authors.lastname: Yano
authors.forename: J
authors.initials: J
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Yasuda
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015282:Octreotide / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D005576:Colforsin; D013004:Somatostatin; C040968:seglitide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015282:Octreotide