Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors

Manuel D. Gahete, Mario Durán-Prado, Elena Delgado-Niebla, Juan J. Garrido, Simon Rhodes, Socorro García-Navarro, Francisco Gracia-Navarro, María M. Malagón, Raúl M. Luque, Justo P. Castaño

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume306
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Somatostatin Receptors
Swine
Somatostatin
Endometriosis
G-Protein-Coupled Receptors
Type 2 Diabetes Mellitus
Primates
Transcription Factors
Genes

Keywords

  • Adenosine 3′,5′-cyclic monophosphate
  • Expression profile
  • Fluorescence resonance energy transfer
  • Heterodimerization
  • Promoter regulation
  • Somatostatin receptor 1

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors. / Gahete, Manuel D.; Durán-Prado, Mario; Delgado-Niebla, Elena; Garrido, Juan J.; Rhodes, Simon; García-Navarro, Socorro; Gracia-Navarro, Francisco; Malagón, María M.; Luque, Raúl M.; Castaño, Justo P.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 306, No. 5, 2014.

Research output: Contribution to journalArticle

Gahete, MD, Durán-Prado, M, Delgado-Niebla, E, Garrido, JJ, Rhodes, S, García-Navarro, S, Gracia-Navarro, F, Malagón, MM, Luque, RM & Castaño, JP 2014, 'Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors', American Journal of Physiology - Endocrinology and Metabolism, vol. 306, no. 5. https://doi.org/10.1152/ajpendo.00587.2013
Gahete, Manuel D. ; Durán-Prado, Mario ; Delgado-Niebla, Elena ; Garrido, Juan J. ; Rhodes, Simon ; García-Navarro, Socorro ; Gracia-Navarro, Francisco ; Malagón, María M. ; Luque, Raúl M. ; Castaño, Justo P. / Porcine sst1 can physically interact with other somatostatin receptors, and its expression is regulated by metabolic/inflammatory sensors. In: American Journal of Physiology - Endocrinology and Metabolism. 2014 ; Vol. 306, No. 5.
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AU - Gahete, Manuel D.

AU - Durán-Prado, Mario

AU - Delgado-Niebla, Elena

AU - Garrido, Juan J.

AU - Rhodes, Simon

AU - García-Navarro, Socorro

AU - Gracia-Navarro, Francisco

AU - Malagón, María M.

AU - Luque, Raúl M.

AU - Castaño, Justo P.

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