Related Experiment Video

Updated: Aug 12, 2026

A Fluorescent Screening Assay for Identifying Modulators of GIRK Channels
05:31

A Fluorescent Screening Assay for Identifying Modulators of GIRK Channels

Published on: April 24, 2012

Agonist-induced phosphorylation of somatostatin receptor subtype 1 (sst1). Relationship to desensitization and

Q Liu1, A Schonbrunn

  • 1Department of Integrative Biology and Pharmacology, University of Texas Health Science Center-Houston, Houston, Texas 77225, USA.

The Journal of Biological Chemistry
|November 14, 2000
PubMed

Insights

The somatostatin (SRIF) receptor subtype 1 (sst1) rapidly desensitizes upon SRIF binding. Receptor phosphorylation, not internalization, drives this desensitization, offering insights into sst1 receptor regulation.

Area of Science:

  • Endocrinology
  • Neuroscience
  • Molecular Pharmacology

Background:

  • The somatostatin (SRIF) receptor subtype 1 (sst1) is broadly expressed across physiological systems and in tumors.
  • Regulation mechanisms for sst1 receptor function remain largely uncharacterized.

Purpose of the Study:

  • To investigate the desensitization, internalization, and phosphorylation of the sst1 receptor.
  • To elucidate the molecular mechanisms underlying sst1 receptor regulation.

Main Methods:

  • Utilized Chinese Hamster Ovary K1 (CHO-K1) cells expressing sst1 receptors.
  • Measured adenylyl cyclase inhibition, receptor-bound ligand internalization, and receptor phosphorylation.
  • Employed mobility shift assays and protein kinase C activators.

Main Results:

  • SRIF treatment rapidly desensitized sst1 receptor function (t(1/2) < 2 min).
  • Receptor phosphorylation increased rapidly (t(1/2) < 2 min) and dose-dependently upon SRIF stimulation.
  • Receptor-bound ligand internalization was a slow process (t(1/2) > 180 min).
  • Phosphorylation was stimulated by the protein kinase C activator, phorbol 12-myristate 13-acetate, and occurred primarily on serine residues.

Conclusions:

  • Sst1 receptor desensitization is primarily mediated by phosphorylation-induced uncoupling.
  • Receptor sequestration (internalization) plays a minimal role in rapid desensitization.
  • These findings provide the first evidence of sst1 receptor phosphorylation and its regulatory role.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
The Two-State Receptor Model01:29

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...