title: Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors.
abstract: The majority of the biological actions attributed to somatostatin (SST) are thought to be mediated by SST receptor 2 (sst2), the most ubiquitous sst, and, to a lesser extent, by sst5. However, a growing body of evidence suggests a relevant role of sst1 in mediating SST actions in (patho)physiological situations (i.e., endometriosis, type 2 diabetes). Moreover, sst1 together with sst2 and sst5 is involved in the well-known actions of SST on pituitary somatotropes in pig and primates. Here, we cloned the porcine sst1 (psst1) and performed a structural and functional characterization using both primary and heterologous models. The psst1 sequence presents the majority of signature motifs shared among G protein-coupled receptors and, specifically, among ssts and exhibits a high homology with other mammalian sst1, with only minor differences in the amino-terminal domain, reinforcing the idea of an early evolutive divergence between mammalian and nonmammalian sst1s. psst1 is functional in terms of decreasing cAMP levels in response to SST when transfected in heterologous models. The psst1 receptor is expressed in several tissues, and analyses of gene cis elements predict regulation by multiple transcription factors and metabolic stimuli. Finally, psst1 is coexpressed with other sst subtypes in various tissues, and in vitro data demonstrate that psst1 can interact with itself forming homodimers and with other ssts forming heterodimers. These data highlight the functional importance of sst1 on the SST-mediated effects and its functional interaction with different ssts, which point out the necessity of exploring the consequences of such interactions.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofia and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, Spain;
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.forename: Mario
authors.initials: M
authors.lastname: Durán-Prado
authors.forename: Elena
authors.initials: E
authors.lastname: Delgado-Niebla
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Garrido
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Rhodes
authors.forename: Socorro
authors.initials: S
authors.lastname: García-Navarro
authors.forename: Francisco
authors.initials: F
authors.lastname: Gracia-Navarro
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
authors.forename: Raúl M
authors.initials: RM
authors.lastname: Luque
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
mesh_terms: D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D013552:Swine
chemical_list: D017481:Receptors, Somatostatin; D013004:Somatostatin
keywords: adenosine 3′,5′-cyclic monophosphate; expression profile; fluorescence resonance energy transfer; heterodimerization; somatostatin receptor 1, promoter regulation