Analog specificity of the thyrotropin-releasing hormone receptor in the central nervous system: possible clinical implications

Journal Article · Mon Feb 11 04:00:00 EST 1985 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(85)90642-3· OSTI ID:5416295

Hawkins, E F; Engel, W K

TRH has rapid-onset (30 sec), slow-offset (1-12 days) clinical benefit in patients with amyotrophic lateral sclerosis and other motor neuron disorders. This benefit is probably receptor-mediated and may have at least 2 components. To obtain a better understanding of the various responses to TRH of the spinal lower motor neurons (LMNs) in patients, and possibly to help guide selection of additional therapeutic agents, the authors utilized rat CNS (spinal-cord and brain membranes) to analyze the ability of certain molecules to inhibit specific binding of (/sup 3/H)methyl TRH ((/sup 3/H)MeTRH) to the TRH receptor. They found: a) lack of high-affinity binding of the TRH-analog DN-1417 by spinal-cord and brain TRH receptor, despite its known strong TRH-like action physiologically on LMNs; b) lack of high-affinity binding of the TRH-product cyclo(His-Pro) by spinal cord and brain TRH receptor despite its having some strong TRH-like physiologic actions on the CNS; and c) lack of any identifiable high-affinity receptor for cyclo(His-Pro) in spinal cord and brain. From these data the authors hypothesize that the acute transmitter-like action of DN-1417, TRH, and possibly other TRH-analogs and products on LMNs is via a non-TRH receptor, such as an amine or amino acid neurotransmitter receptor, e.g. a 5-hydroxytryptamine receptor. They further postulate that the CNS TRH-receptor may modulate a trophic-like influence of TRH on LMNs.

• Research Organization: Univ. of Southern California School of Medicine, Los Angeles
• OSTI ID: 5416295
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 36:6; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMAL CELLS
ANIMALS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHEMICAL BONDS
HORMONES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
NERVE CELLS
NERVOUS SYSTEM
PATIENTS
PEPTIDE HORMONES
RATS
RECEPTORS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
TRH
TRITIUM COMPOUNDS
VERTEBRATES