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Related Experiment Videos

The parathyroid hormone 2 (PTH2) receptor.

T B Usdin1, T I Bonner, S R J Hoare

  • 1Laboratory of Genetics, National Institute of Mental Health, Building 36/Room 3D06, 36 Convent Drive, Bethesda, Maryland 20892-4094, USA. usdin@codon.nih.gov

Receptors & Channels
|January 18, 2003
PubMed
Summary

Tuberoinfundibular peptide of 39 residues (TIP39) may be the natural ligand for the human PTH2 receptor, activating it with high potency. The PTH2 receptor is primarily found in the nervous system and pancreatic islet cells.

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Parathyroid hormone 2 receptor and its endogenous ligand tuberoinfundibular peptide of 39 residues are concentrated in endocrine, viscerosensory and auditory brain regions in macaque and human.

Neuroscience·2009

Area of Science:

  • Endocrinology
  • Neuroscience
  • Molecular Biology

Background:

  • The parathyroid hormone 2 (PTH2) receptor is a G protein-coupled receptor involved in various physiological processes.
  • While parathyroid hormone (PTH) activates the PTH1 receptor, its interaction with the PTH2 receptor is less potent.
  • The discovery of tuberoinfundibular peptide of 39 residues (TIP39) suggests a potential natural ligand for the PTH2 receptor.

Purpose of the Study:

  • To investigate the ligand binding and activation properties of the human PTH2 receptor.
  • To compare the activity of TIP39 and PTH on the PTH2 receptor.
  • To elucidate the distribution and potential functions of the PTH2 receptor in the human body.

Main Methods:

  • Ligand binding assays to determine affinity and potency.

Related Experiment Videos

  • Second messenger assays (cAMP and intracellular calcium) to assess receptor activation.
  • In situ hybridization or immunohistochemistry to determine receptor distribution.

    • Main Results:

    • The human PTH2 receptor is activated at high potency by TIP39 and PTH.
    • Rat and zebrafish PTH2 receptors are activated more weakly by PTH, supporting TIP39 as the natural ligand.
    • The PTH2 receptor shows minimal interaction with parathyroid hormone-related peptide (PTHrP).
    • Receptor activation is strongly coupled to cAMP accumulation and weakly to intracellular calcium increases.
    • The PTH2 receptor is predominantly expressed in the nervous system (cerebral cortex, basal ganglia, septum, thalamus, hypothalamus, spinal cord) and pancreatic islet somatostatin cells.

    Conclusions:

    • TIP39 is likely the endogenous ligand for the human PTH2 receptor.
    • The PTH2 receptor's signaling involves cAMP and calcium pathways.
    • The widespread distribution in the nervous system suggests roles in neuroendocrine function and pain modulation.
    • Peripheral expression in pancreatic islets indicates potential roles in metabolic regulation.