Abstract 559 Poster Session I, Saturday, 5/1 (poster 290)
The diverse biological effects of somatostatin (sst) are mediated through a family of G protein coupled receptors, of which 5 members have been recently identified by molecular cloning. mRNA for somatostatin-receptor 1-5 (sst-5) are widely expressed in brain and peripheral organs and display an overlapping but characteristic pattern that is subtype-selective and tissue-specific.
We investigated the endocytosis of sst1 and sst3 after binding of somatostatin-14. sst1 and sst3 were expressed in the neuroendocrine cell line RIN 1046-38 with or without epitope tags at their carboxytermini.
Application of somatostatin-14 at 37°C, but not at 4°C, to cells transfected with sst1 or sst3 cDNA resulted in a significant decrease of cell surface binding sites for 125T-Tyr11-somatostatin-14. Confocal microscopy revealed that sst1-mediated fluorescein-labeled somatostatin-14 was preferentially taken up into plasma membrane-associated structures.
In contrast, sst3-mediated fluorescein-labeled somatostatin-14 was localized in perinuclear compartments.
Investigation of the kinetics of both pathways of internalisation showed that only the sst3-mediated internalization leads to a rapid and complete degradation of the peptide; in contrast, the sst1-mediated internalization is followed by a recycling of the intact peptide into the cell medium.
Chronic stimulation of the sst1 with somatostatin -14 had no effect on the recycling of the receptor after removal of the ligand. In contrast, chronic stimulation of sst3 led to a decrease of the recycled receptors. Both receptor subtypes are endocytosed via different pathways. sst3 internalized via the elathrin-coated vesicle pathway. We speculate that sst1 is internalized via caveolin-like structures and that the characteristics of this pathway are coupled to the physiological function of this autoreceptor.
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(Spon by: S Hawgood)
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Roosterman, D., Stevens, P. & Meyerhof, W. Different Pathways of Internalization of the Somatostatin Receptor sst3 and the Possible Autoreceptor sst1. Pediatr Res 45, 97 (1999). https://doi.org/10.1203/00006450-199904020-00576
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DOI: https://doi.org/10.1203/00006450-199904020-00576
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