Parathyroid hormone binding sites in the brain.
Parathyroid hormone (PTH) has been shown to have actions within the brain, suggesting the presence of central PTH receptors. This possibility was examined by determining the binding of 125I-labeled [Nle8,18,Tyr34]bovine PTH to the plasma membranes of rat and rabbit brains. Specific binding of the tracer to membranes of the whole brain was time and tissue dependent, and was greater with membranes from the hypothalamus than with membranes from the cerebellum, cerebrum, or brain stem. The binding of the tracer to rat hypothalamic membranes was saturable and competitively displaced by unlabeled PTH(1-34), PTH(3-34), [Nle8,18,Tyr34]PTH(1-34), and by PTH-related protein, indicating the presence of a single class of high-affinity (dissociation constant = 2-5 nM), low-capacity (maximum binding capacity, Bmax = 110-250 fmol/mg protein) binding site. The binding of radiolabeled PTH to these sites was not displaced by unrelated peptides of comparable molecular size (calcitonin, calcitonin-gene related peptide, adrenocorticotropin). The binding of PTH to these sites did not, however, appear to stimulate adenylate cyclase activity, as in peripheral PTH target sites. Thus, although these results indicate the presence of PTH receptors in the brain, these binding sites have a lower affinity than those in peripheral tissues and may utilize a different signal transduction system.
Harvey
S
S
Department of Physiology, University of Alberta, Edmonton, Canada.
Hayer
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S
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018016:Receptors, Parathyroid Hormone / Q000032:analysis*
D018016:Receptors, Parathyroid Hormone; D000262:Adenylyl Cyclases