We are studying the secretin-VIP family of G-protein coupled receptors. This recently identified group of receptors has virtually no amino acid sequence conservation with the remaining majority of G-protein coupled receptors (the rhodopsin family). Much less is known about structure- function relationships and effector system coupling of the secretin-VIP family receptors. Their cloning has also raised new questions about their physiological roles and created tools for study of their distribution, regulation and pharmacology. Previously we identified the receptor for GIP. This has facilitated the study of GIP's involvement in peripheral glucose homeostasis. Our collaborator Mike Wolfe (Gastroenterology Div. Brigham and Womens Hospital) used a GIP reporter cell we generated to develop a GIP receptor antagonist and used this antagonist to demonstrate in rats that GIP is a major mediator of the immediate insulin response to feeding. We recently discovered a new receptor which recognizes parathyroid hormone, which we have named the PTH2 receptor. We have now further characterized the pharmacological properties of the PTH2 receptor and studied its distribution. In collaboration with the Endocrine Unit at Mass. General Hospital we identified the amino acid residues in parathyroid hormone-related peptide (PTHrP) which allow the PTH2 receptor to discriminate between PTH and PTHrP. Mapping the distribution of PTH2 receptor mRNA suggests that it may play a role in a number of physiological systems including blood pressure control. In the CNS it appears to be present in hippocampal input and output circuits. We have preliminary evidence for a new bioactive peptide in brain extracts which acts at the PTH2 receptor and are now working on a detailed characterization and purification of that peptide.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002685-03
Application #
2578818
Study Section
Special Emphasis Panel (LCB)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Brenner, David; Bago, Attila G; Gallatz, Katalin et al. (2008) Tuberoinfundibular peptide of 39 residues in the embryonic and early postnatal rat brain. J Chem Neuroanat 36:59-68
Bago, Attila G; Palkovits, Miklos; Usdin, Ted B et al. (2008) Evidence for the expression of parathyroid hormone 2 receptor in the human brainstem. Ideggyogy Sz 61:123-6
Usdin, Ted B; Paciga, Mark; Riordan, Tim et al. (2008) Tuberoinfundibular Peptide of 39 residues is required for germ cell development. Endocrinology 149:4292-300
Fegley, D B; Holmes, A; Riordan, T et al. (2008) Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues. Genes Brain Behav 7:933-42
Faber, Catherine A; Dobolyi, Arpad; Sleeman, Mark et al. (2007) Distribution of tuberoinfundibular peptide of 39 residues and its receptor, parathyroid hormone 2 receptor, in the mouse brain. J Comp Neurol 502:563-83
Kuo, Jonathan; Usdin, Ted B (2007) Development of a rat parathyroid hormone 2 receptor antagonist. Peptides 28:887-92
Dobolyi, Arpad; Irwin, Sarah; Wang, Jing et al. (2006) The distribution and neurochemistry of the parathyroid hormone 2 receptor in the rat hypothalamus. Neurochem Res 31:227-36
Wang, J; Palkovits, M; Usdin, T B et al. (2006) Forebrain projections of tuberoinfundibular peptide of 39 residues (TIP39)-containing subparafascicular neurons. Neuroscience 138:1245-63
Dobolyi, Arpad; Wang, Jing; Irwin, Sarah et al. (2006) Postnatal development and gender-dependent expression of TIP39 in the rat brain. J Comp Neurol 498:375-89
Wang, J; Palkovits, M; Usdin, T B et al. (2006) Afferent connections of the subparafascicular area in rat. Neuroscience 138:197-220

Showing the most recent 10 out of 44 publications