The role of limited proteolysis of thyrotropin-releasing hormone in thermoregulation. Final report
Cyclo (His-Pro) is a biologiclly active cyclic dipeptide derived from thyrotropin-releasing hormone by its limited proteolysis. We have developed a specific radioimmunoassay for this cyclic peptide and shown its presence throughout rat and monkey brains. The normal rat brain concentration of cyclo (His-Pro) ranged from 35-61 pmols/brain. The elution profiles of rat brain cyclo (His-Pro)-like immunoreactivity and synthetic radioactive cyclo (His-Pro) following gel filtration, ion-exchange chromatography and high pressure liquid chromatography were similar. An analysis of the regional distribution of cyclo (His-Pro) and TRH in rat and monkey brains exhibited no apparent precursor-product relationship. Studies on the neuroanatomic sites for the thermoregulatory effects of cyclo (His-Pro) suggested that the neural loci responsible for cyclo (His-Pro)-induced hypothermia resides within POA/AHA. The endogenous levels of brain cyclo (His-Pro) were elevated when rats were made either hypothyroid by surgical thyroidectomy or forced to drink alcohol for six weeks. These studies demonstrate that cyclo (His-Pro) is present throughout the central nervous system in physiologically relevant concentrations which can be modified by appropriate physiological and pharamacological manipulations. These data in conjunction with earlier reports of multiple biological activities of exogenous cyclo (His-Pro), suggest that endogenous cyclo (His-Pro) is a biological active peptide and it may play a neurotransmitter or neuromodulator role in the central nervous system.
- Research Organization:
- Louisiana State Univ., New Orleans (USA). Medical Center
- OSTI ID:
- 6531793
- Report Number(s):
- AD-A-119425/7
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
PEPTIDES
RADIOIMMUNOASSAY
TISSUE DISTRIBUTION
PITUITARY HORMONES
PROTEOLYSIS
ANTIBODIES
BIOSYNTHESIS
BODY TEMPERATURE
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
FILTRATION
HYPERTHERMIA
HYPOTHALAMUS
HYPOTHERMIA
INJECTION
MONKEYS
PRECURSOR
PROTEINS
RATS
THERMOREGULATION
ANIMALS
BODY
BRAIN
CHEMICAL REACTIONS
CONTROL
DECOMPOSITION
DISTRIBUTION
HORMONES
INTAKE
ISOTOPE APPLICATIONS
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PRIMATES
RADIOASSAY
RODENTS
SEPARATION PROCESSES
SYNTHESIS
TEMPERATURE CONTROL
TRACER TECHNIQUES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550201 - Biochemistry- Tracer Techniques