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TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus

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Abstract

Activation by parathyroid hormone (PTH)1 and peripheral distribution2,3 the of PTH2 receptor (PTH2-R) are well described. Highest expression of PTH2-R is found in the brain1, where PTH synthesis is undetectable. We have now purified and sequenced a new polypeptide from bovine hypothalamus (referred to here as tuberoinfundibular peptide of 39 residues; TIP39), a potent and selective agonist at the PTH2-R. The PTH2-R was highly expressed in hypothalamic areas that regulate pituitary hormone secretion and spinal cord regions involved in pain perception.

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Figure 1: Purification of the PTH2 receptor-activating peptide.
Figure 2: Comparison of receptor activation by synthetic TIP39 and PTH analogs.
Figure 3: CNS PTH2-receptor expression.

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Acknowledgements

Large-scale tissue extraction was performed by Thomas McCloud and Andrew Burnette of the National Cancer Institute Natural Products Support Group and microsequencing by the Harvard University Microchemistry Facility. TIP39 was synthesized by AnaSpec, Inc. F-11 and N18TG2 cells were obtained from H. Gainer. We thank Chris Evans, Lisa Baptiste, Ed Unsworth and Howard Jaffe for advice and assistance and Mike Brownstein and Hal Gainer for reviewing the manuscript.

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Authors and Affiliations

  1. Unit on Cell Biology, Laboratory of Genetics, National Institute of Mental Health, Building 36/Room 3D06, 36 Convent Drive MSC4094, Bethesda, 20892-4094, Maryland, USA

    T. B. Usdin, S. R. J. Hoare & T. Wang

  2. Basic Neuroscience Program, National Institute of Neurological Diseases and Stroke, Building 36/Room 3D06, 36 Convent Drive MSC4094, Bethseda, 20892-4094, Maryland, USA

    É. Mezey

  3. Laboratory of Neurotoxicology, National Institute of Mental Health, Building 10/Room 3D42, 10 Center Drive MSC1262, Bethseda, 20892-1262, Maryland, USA

    J. A. Kowalak

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  1. T. B. Usdin
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  2. S. R. J. Hoare
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  3. T. Wang
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  4. É. Mezey
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  5. J. A. Kowalak
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Correspondence to T. B. Usdin.

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Usdin, T., Hoare, S., Wang, T. et al. TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci 2, 941–943 (1999). https://doi.org/10.1038/14724

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  • DOI: https://doi.org/10.1038/14724

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