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Evidence for a Parathyroid Hormone-2 Receptor Selective Ligand in the Hypothalamus

National Institute of Mental Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Ted B. Usdin, National Institute of Mental Health, Building 36, Room 3A17, 36 Convent Drive, Bethesda, Maryland 20892.

The PTH2 receptor is expressed in several brain nuclei but we have been unable to detect mRNA encoding PTH, which is the only known ligand for the PTH2 receptor, in the brain. We now have evidence for a PTH2 receptor selective ligand in an acid-acetone extract made from bovine hypothalamus. The partially purified extract activates the PTH2 receptor more effectively than it activates the PTH/PTHrP receptor, while PTH activates these two receptors at similar concentration. The activity appears immunologically distinct from PTH and its effect is potently antagonized by [D-Trp¹²]bPTH(7-34). These data provide evidence for a biologically active peptide, which may be related to PTH, and which is a potential new neurotransmitter or hormone.

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