Diversity of Thyrotropin-Releasing Hormone Receptors in the Pituitaryand Discrete Brain Regions of Rats

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Author(s)

Abstract

In order to analyze the receptor properties of central nervous system (CNS)-stimulant thyrotropin-releasing hormone (L-pyroglutamyl-L-histidyl-L-prolinamide, TRH), we evaluated the binding of TRH and its analog taltirelin hydrate ((-)-<I>N</I>-[(<I>S</I>)-hexahydro-1-methyl-2, 6-dioxo-4-pyrimidinylcarbonyl]-L-histidyl-L-prolinamide tetrahydrate; taltirelin, TA-0910) in rat anterior pituitary and several brain regions. There was a specific binding of [<SUP>3</SUP>H]methyl TRH (MeTRH) in the anterior pituitary, hypothalamus, brain stem, cerebral cortex and cerebellum with K<SUB>d</SUB> values of 1.0 - 1.6 nM. The inhibition of [<SUP>3</SUP>H]MeTRH binding by TRH and taltirelin was monophasic in the anterior pituitary, hypothalamus and brain stem with K<SUB>i</SUB> values of 6.3 - 8.0 nM and 145.5 - 170.4 nM for TRH and taltirelin, respectively. In contrast, the biphasic inhibition was revealed in the cerebral cortex and cerebellum. The K<SUB>i</SUB> values for TRH and taltirelin were 4.1 - 4.3 nM and 67.8 - 73.4 nM for the high affinity binding site and 3.6 - 4.2 μM and 82.3 - 197.5 μM for the low affinity binding site, respectively. Addition of 100 μM GTP or its analog 5′-guanylylimidodiphosphate (Gpp[NH]p) affected neither the biphasic inhibition by TRH nor that by taltirelin. Thus the results suggest the presence of distinct high and low affinity TRH receptors in the CNS in contrast to the pituitary.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 79(3), 313-317, 1999-03-01

    The Japanese Pharmacological Society

References:  21

Codes

  • NII Article ID (NAID)
    10008682784
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    REV
  • ISSN
    00215198
  • NDL Article ID
    4699235
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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